The KKS power plant identification system. 3. ed.

International Nuclear Information System (INIS)

1988-01-01

The previous first and second editions of the KKS, system for power plant identification, consisted of the following: introduction; instructions for application with a comparative presentation of the DIN/KKS systems and subject index; keys (functional key, equipment key, operating media key). The third edition now available incorporates the following revisions and additions: instructions for application refer exclusively to the KKS system; key updates; revised coordinating file for the equipment key and operating media key; a completely new section entitled 'Agreements for coordination of project activities', in an annex to the KKS instructions; comparison DIN/KKS adapted to new version of KKS instructions; the subject index of the 2nd edition has been extended by a keyword index referring to the explanations for application of the KKS system. (orig./HP) [de

Kallikrein and Renin in the Membrane Fractions of the Rat Kidney.

Science.gov (United States)

1980-05-23

fraction. PM-kallikrein re- leased a kinin, cleaved the peptide substrate, S-2266 and a radio-labeled arginine ester. The ester was also hydrolyzed by renal...more by activators of kallikrein, e.g. by phospholipase A/, lyso- lecithin and melittin. Low sodium diet increased the activity of kallikrein in the...peptide substrate, S-2266 and a radio- labeled arginine ester. The ester was also hydrolyzed by renal enzymes other than kallikrein. PM-kallikrein was

Identification, purification, and localization of tissue kallikrein in rat heart.

OpenAIRE

Xiong, W; Chen, L M; Woodley-Miller, C; Simson, J A; Chao, J

1990-01-01

A tissue kallikrein has been isolated from rat heart extracts by DEAE-Sepharose and aprotinin-affinity column chromatography. The purified cardiac enzyme has both N-tosyl-L-arginine methyl ester esterolytic and kinin-releasing activities, and displays parallelism with standard curves in a kallikrein radioimmunoassay, indicating it to have immunological identity with tissue kallikrein. The enzyme is inhibited by aprotinin, antipain, leupeptin and by high concentrations of soybean trypsin inhib...

Mast Cell Coupling to the Kallikrein–Kinin System Fuels Intracardiac Parasitism and Worsens Heart Pathology in Experimental Chagas Disease

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Clarissa R. Nascimento

2017-08-01

Full Text Available During the course of Chagas disease, infectious forms of Trypanosoma cruzi are occasionally liberated from parasitized heart cells. Studies performed with tissue culture trypomastigotes (TCTs, Dm28c strain demonstrated that these parasites evoke neutrophil/CXCR2-dependent microvascular leakage by activating innate sentinel cells via toll-like receptor 2 (TLR2. Upon plasma extravasation, proteolytically derived kinins and C5a stimulate immunoprotective Th1 responses via cross-talk between bradykinin B2 receptors (B2Rs and C5aR. Awareness that TCTs invade cardiovascular cells in vitro via interdependent activation of B2R and endothelin receptors [endothelin A receptor (ETAR/endothelin B receptor (ETBR] led us to hypothesize that T. cruzi might reciprocally benefit from the formation of infection-associated edema via activation of kallikrein–kinin system (KKS. Using intravital microscopy, here we first examined the functional interplay between mast cells (MCs and the KKS by topically exposing the hamster cheek pouch (HCP tissues to dextran sulfate (DXS, a potent “contact” activator of the KKS. Surprisingly, although DXS was inert for at least 30 min, a subtle MC-driven leakage resulted in factor XII (FXII-dependent activation of the KKS, which then amplified inflammation via generation of bradykinin (BK. Guided by this mechanistic insight, we next exposed TCTs to “leaky” HCP—forged by low dose histamine application—and found that the proinflammatory phenotype of TCTs was boosted by BK generated via the MC/KKS pathway. Measurements of footpad edema in MC-deficient mice linked TCT-evoked inflammation to MC degranulation (upstream and FXII-mediated generation of BK (downstream. We then inoculated TCTs intracardiacally in mice and found a striking decrease of parasite DNA (quantitative polymerase chain reaction; 3 d.p.i. in the heart of MC-deficient mutant mice. Moreover, the intracardiac parasite load was significantly reduced in WT

KKS:The new power plant characterisation system in practice

International Nuclear Information System (INIS)

Becker, G.; Bohr, E.; Wildberg, D.

1982-01-01

These use of the new power plant characterisation system (KKS) in power plant operation is discussed. KKS intends to ensure reliable characterisation of plant components. It must be read, interpreted, communicated directly or by telephone and written down. An analysis under the aspects of information psychology and ergonomy has shown that the findings of ergonomy and information psychology have hardly been considerd in the design of KKS. The conclusions of this analysis are investigated with regard to their consequences for KKS application in power plant operation. Possibilities of improvement are discussed. (orig./HP) [de

Mycoplasma hyopneumoniae in vitro peptidase activities: identification and cleavage of kallikrein-kinin system-like substrates.

Science.gov (United States)

Moitinho-Silva, Lucas; Kondo, Marcia Y; Oliveira, Lilian C G; Okamoto, Debora N; Paes, Jéssica A; Machado, Mauricio F M; Veronez, Camila L; Motta, Guacyara; Andrade, Sheila S; Juliano, Maria A; Ferreira, Henrique B; Juliano, Luiz; Gouvea, Iuri E

2013-05-03

Bacterial proteases are important for metabolic processes and pathogenesis in host organisms. The bacterial swine pathogen Mycoplasma hyopneumoniae has 15 putative protease-encoding genes annotated, but none of them have been functionally characterized. To identify and characterize peptidases that could be relevant for infection of swine hosts, we investigated the peptidase activity present in the pathogenic 7448 strain of M. hyopneumoniae. Combinatorial libraries of fluorescence resonance energy transfer peptides, specific inhibitors and pH profiling were used to screen and characterize endopeptidase, aminopeptidase and carboxypeptidase activities in cell lysates. One metalloendopeptidase, one serine endopeptidase, and one aminopeptidase were detected. The detected metalloendopeptidase activity, prominent at neutral and basic pH ranges, was due to a thimet oligopeptidase family member (M3 family), likely an oligoendopeptidase F (PepF), which cleaved the peptide Abz-GFSPFRQ-EDDnp at the F-S bond. A chymotrypsin-like serine endopeptidase activity, possibly a subtilisin-like serine protease, was prominent at higher pH levels, and was characterized by its preference for a Phe residue at the P1 position of the substrate. The aminopeptidase P (APP) activity showed a similar profile to that of human membrane-bound APP. Genes coding for these three peptidases were identified and their transcription was confirmed in the 7448 strain. Furthermore, M. hyopneumoniae cell lysate peptidases showed effects on kallikrein-kinin system-like substrates, such as bradykinin-derived substrates and human high molecular weight kininogen. The M. hyopneumoniae peptidase activities, here characterized for the first time, may be important for bacterial survival strategies and thus represent possible targets for drug development against M. hyopneumoniae swine infections. Copyright © 2013 Elsevier B.V. All rights reserved.

Protease Inhibitors Extracted from Caesalpinia echinata Lam. Affect Kinin Release during Lung Inflammation

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Ilana Cruz-Silva

2016-01-01

Full Text Available Inflammation is an essential process in many pulmonary diseases in which kinins are generated by protease action on kininogen, a phenomenon that is blocked by protease inhibitors. We evaluated kinin release in an in vivo lung inflammation model in rats, in the presence or absence of CeKI (C. echinata kallikrein inhibitor, a plasma kallikrein, cathepsin G, and proteinase-3 inhibitor, and rCeEI (recombinant C. echinata elastase inhibitor, which inhibits these proteases and also neutrophil elastase. Wistar rats were intravenously treated with buffer (negative control or inhibitors and, subsequently, lipopolysaccharide was injected into their lungs. Blood, bronchoalveolar lavage fluid (BALF, and lung tissue were collected. In plasma, kinin release was higher in the LPS-treated animals in comparison to CeKI or rCeEI groups. rCeEI-treated animals presented less kinin than CeKI-treated group. Our data suggest that kinins play a pivotal role in lung inflammation and may be generated by different enzymes; however, neutrophil elastase seems to be the most important in the lung tissue context. These results open perspectives for a better understanding of biological process where neutrophil enzymes participate and indicate these plant inhibitors and their recombinant correlates for therapeutic trials involving pulmonary diseases.

Immunochemical Studies of Plasma Kallikrein

Science.gov (United States)

Bagdasarian, Andranik; Lahiri, Biswajit; Talamo, Richard C.; Wong, Pat; Colman, Robert W.

1974-01-01

A monospecific antibody against human plasma kallikrein has been prepared in rabbits with kallikrein further purified to remove gamma globulins. The antisera produced contained antikallikrein and also anti-IgG, in spite of only 8% contamination of kallikrein preparation with IgG. The latter antibody was removed by adsorption of antisera with either Fletcher factor-deficient plasma or with purified IgG. Both kallikrein and prekallikrein (in plasma) cross-react with the antibody with no apparent difference between the precipitation arcs developed during immunoelectrophoresis and no significant difference in reactivity when quantified by radial immunodiffusion. Kallikrein antibody partially inhibits the esterolytic and fully inhibits the proteolytic activity of kallikrein. In addition, the antibody inhibits the activation of prekallikrein, as measured by esterase or kinin release. The magnitude of the inhibition is related to the molecular weight of the activator used. Thus, for the four activators tested, the greatest inhibition is observed with kaolin and factor XIIA, while large activator and the low molecular weight prekallikrein activators are less inhibited. With the kallikrein antibody, the incubation of kallikrein with either plasma or partially purified C1 esterase inactivator results in a new precipitin arc, as detected by immunoelectrophoresis. This finding provides physical evidence for the interaction of the enzyme and inhibitor. No new arc could be demonstrated between kallikrein and α2-macroglobulin, or α1-antitrypsin, although the concentration of free kallikrein antigen decreases after interaction with the former inhibitor. By radial immunodiffusion, plasma from healthy individuals contained 103±13 μg/ml prekallikrein antigen. Although in mild liver disease, functional and immunologic kallikrein are proportionally depressed, the levels of prekallikrein antigen in plasma samples from patients with severe liver disease remains 40% of normal, while

SMART-KKS. Chances and economic efficiency; SMART-KKS. Chancen und Wirtschaftlichkeit

Energy Technology Data Exchange (ETDEWEB)

Deiss, Rainer [EnBW Regional AG, Stuttgart (Germany); Buechler, Markus [Schweizerische Gesellschaft fuer Korrosionsschutz, Zuerich (Switzerland); Naleppa, Stefan [RBS wave GmbH, Stuttgart (Germany)

2011-07-01

Future demands on KKS cannot be met by the current remote monitoring technology. New remote monitoring concepts and smart protective current concepts will be required to make KKS more economical and more reliable. The contribution presents new findings on AC corrosion in order to show how future KKS technology may be designed.

Glycosaminoglycans affect the interaction of human plasma kallikrein with plasminogen, factor XII and inhibitors

Directory of Open Access Journals (Sweden)

Gozzo A.J.

2003-01-01

Full Text Available Human plasma kallikrein, a serine proteinase, plays a key role in intrinsic blood clotting, in the kallikrein-kinin system, and in fibrinolysis. The proteolytic enzymes involved in these processes are usually controlled by specific inhibitors and may be influenced by several factors including glycosaminoglycans, as recently demonstrated by our group. The aim of the present study was to investigate the effect of glycosaminoglycans (30 to 250 µg/ml on kallikrein activity on plasminogen and factor XII and on the inhibition of kallikrein by the plasma proteins C1-inhibitor and antithrombin. Almost all available glycosaminoglycans (heparin, heparan sulfate, bovine and tuna dermatan sulfate, chondroitin 4- and 6-sulfates reduced (1.2 to 3.0 times the catalytic efficiency of kallikrein (in a nanomolar range on the hydrolysis of plasminogen (0.3 to 1.8 µM and increased (1.9 to 7.7 times the enzyme efficiency in factor XII (0.1 to 10 µM activation. On the other hand, heparin, heparan sulfate, and bovine and tuna dermatan sulfate improved (1.2 to 3.4 times kallikrein inhibition by antithrombin (1.4 µM, while chondroitin 4- and 6-sulfates reduced it (1.3 times. Heparin and heparan sulfate increased (1.4 times the enzyme inhibition by the C1-inhibitor (150 nM.

An interaction of renin-angiotensin and kallikrein-kinin systems contributes to vascular hypertrophy in angiotensin II-induced hypertension: in vivo and in vitro studies.

Directory of Open Access Journals (Sweden)

Graziela S Ceravolo

Full Text Available The kallikrein-kinin and renin-angiotensin systems interact at multiple levels. In the present study, we tested the hypothesis that the B1 kinin receptor (B1R contributes to vascular hypertrophy in angiotensin II (ANG II-induced hypertension, through a mechanism involving reactive oxygen species (ROS generation and extracellular signal-regulated kinase (ERK1/2 activation. Male Wistar rats were infused with vehicle (control rats, 400 ng/Kg/min ANG II (ANG II rats or 400 ng/Kg/min ANG II plus B1 receptor antagonist, 350 ng/Kg/min des-Arg(9-Leu(8-bradykinin (ANGII+DAL rats, via osmotic mini-pumps (14 days or received ANG II plus losartan (10 mg/Kg, 14 days, gavage - ANG II+LOS rats. After 14 days, ANG II rats exhibited increased systolic arterial pressure [(mmHg 184 ± 5.9 vs 115 ± 2.3], aortic hypertrophy; increased ROS generation [2-hydroxyethidium/dihydroethidium (EOH/DHE: 21.8 ± 2.7 vs 6.0 ± 1.8] and ERK1/2 phosphorylation (% of control: 218.3 ± 29.4 vs 100 ± 0.25]. B1R expression was increased in aortas from ANG II and ANG II+DAL rats than in aortas from the ANG II+LOS and control groups. B1R antagonism reduced aorta hypertrophy, prevented ROS generation (EOH/DHE: 9.17 ± 3.1 and ERK1/2 phosphorylation (137 ± 20.7% in ANG II rats. Cultured aortic vascular smooth muscle cells (VSMC stimulated with low concentrations (0.1 nM of ANG II plus B1R agonist exhibited increased ROS generation, ERK1/2 phosphorylation, proliferating-cell nuclear antigen expression and [H3]leucine incorporation. At this concentration, neither ANG II nor the B1R agonist produced any effects when tested individually. The ANG II/B1R agonist synergism was inhibited by losartan (AT1 blocker, 10 µM, B1R antagonist (10 µM and Tiron (superoxide anion scavenger, 10 mM. These data suggest that B1R activation contributes to ANG II-induced aortic hypertrophy. This is associated with activation of redox-regulated ERK1/2 pathway that controls aortic smooth muscle cells growth

Amelioration of cardiac function and activation of anti-inflammatory vasoactive peptides expression in the rat myocardium by low level laser therapy.

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Martha Trindade Manchini

Full Text Available Low-level laser therapy (LLLT has been used as an anti-inflammatory treatment in several disease conditions, even when inflammation is a secondary consequence, such as in myocardial infarction (MI. However, the mechanism by which LLLT is able to protect the remaining myocardium remains unclear. The present study tested the hypothesis that LLLT reduces inflammation after acute MI in female rats and ameliorates cardiac function. The potential participation of the Renin-Angiotensin System (RAS and Kallikrein-Kinin System (KKS vasoactive peptides was also evaluated. LLLT treatment effectively reduced MI size, attenuated the systolic dysfunction after MI, and decreased the myocardial mRNA expression of interleukin-1 beta and interleukin-6 in comparison to the non-irradiated rat tissue. In addition, LLLT treatment increased protein and mRNA levels of the Mas receptor, the mRNA expression of kinin B2 receptors and the circulating levels of plasma kallikrein compared to non-treated post-MI rats. On the other hand, the kinin B1 receptor mRNA expression decreased after LLLT. No significant changes were found in the expression of vascular endothelial growth factor (VEGF in the myocardial remote area between laser-irradiated and non-irradiated post-MI rats. Capillaries density also remained similar between these two experimental groups. The mRNA expression of the inducible nitric oxide synthase (iNOS was increased three days after MI, however, this effect was blunted by LLLT. Moreover, endothelial NOS mRNA content increased after LLLT. Plasma nitric oxide metabolites (NOx concentration was increased three days after MI in non-treated rats and increased even further by LLLT treatment. Our data suggest that LLLT diminishes the acute inflammation in the myocardium, reduces infarct size and attenuates left ventricle dysfunction post-MI and increases vasoactive peptides expression and nitric oxide (NO generation.

Amelioration of Cardiac Function and Activation of Anti-Inflammatory Vasoactive Peptides Expression in the Rat Myocardium by Low Level Laser Therapy

Science.gov (United States)

Manchini, Martha Trindade; Serra, Andrey Jorge; Feliciano, Regiane dos Santos; Santana, Eduardo Tadeu; Antônio, Ednei Luis; de Tarso Camillo de Carvalho, Paulo; Montemor, Jairo; Crajoinas, Renato Oliveira; Girardi, Adriana Castello Costa; Tucci, Paulo José Ferreira; Silva, José Antônio

2014-01-01

Low-level laser therapy (LLLT) has been used as an anti-inflammatory treatment in several disease conditions, even when inflammation is a secondary consequence, such as in myocardial infarction (MI). However, the mechanism by which LLLT is able to protect the remaining myocardium remains unclear. The present study tested the hypothesis that LLLT reduces inflammation after acute MI in female rats and ameliorates cardiac function. The potential participation of the Renin-Angiotensin System (RAS) and Kallikrein-Kinin System (KKS) vasoactive peptides was also evaluated. LLLT treatment effectively reduced MI size, attenuated the systolic dysfunction after MI, and decreased the myocardial mRNA expression of interleukin-1 beta and interleukin-6 in comparison to the non-irradiated rat tissue. In addition, LLLT treatment increased protein and mRNA levels of the Mas receptor, the mRNA expression of kinin B2 receptors and the circulating levels of plasma kallikrein compared to non-treated post-MI rats. On the other hand, the kinin B1 receptor mRNA expression decreased after LLLT. No significant changes were found in the expression of vascular endothelial growth factor (VEGF) in the myocardial remote area between laser-irradiated and non-irradiated post-MI rats. Capillaries density also remained similar between these two experimental groups. The mRNA expression of the inducible nitric oxide synthase (iNOS) was increased three days after MI, however, this effect was blunted by LLLT. Moreover, endothelial NOS mRNA content increased after LLLT. Plasma nitric oxide metabolites (NOx) concentration was increased three days after MI in non-treated rats and increased even further by LLLT treatment. Our data suggest that LLLT diminishes the acute inflammation in the myocardium, reduces infarct size and attenuates left ventricle dysfunction post-MI and increases vasoactive peptides expression and nitric oxide (NO) generation. PMID:24991808

Kallikrein-like amidase activity in renal ischemia and reperfusion

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M.D. Carattino

2000-05-01

Full Text Available We assessed a kallikrein-like amidase activity probably related to the kallikrein-kinin system, as well as the participation of leukocyte infiltration in renal ischemia and reperfusion. Male C57BL/KSJmdb mice were subjected to 20 or 60 min of ischemia and to different periods of reperfusion. A control group consisted of sham-operated mice, under similar conditions, except for ischemia induction. Kallikrein-like amidase activity, Evans blue extravasation and myeloperoxidase activity were measured in kidney homogenates, previously perfused with 0.9% NaCl. Plasma creatinine concentration increased only in the 60-min ischemic group. After 20 min of ischemia and 1 or 24 h of reperfusion, no change in kallikrein-like amidase activity or Evans blue extravasation was observed. In the mice subjected to 20 min of ischemia, edema was evident at 1 h of reperfusion, but kidney water content returned to basal levels after 24 h of reperfusion. In the 60-min ischemic group, kallikrein-like amidase activity and Evans blue extravasation showed a similar significant increase along reperfusion time. Kallikrein-like amidase activity increased from 4 nmol PNA mg protein-1 min-1 in the basal condition to 15 nmol PNA mg protein-1 min-1 at 10 h of reperfusion. For dye extravasation the concentration measured was near 200 µg of Evans blue/g dry tissue in the basal condition and 1750 µg of Evans blue/g dry tissue at 10 h of reperfusion. No variation could be detected in the control group. A significant increase from 5 to 40 units of DAbs 655 nm g wet tissue-1 min-1 in the activity of the enzyme myeloperoxidase was observed in the 60-min ischemic group, when it was evaluated after 24 h of reperfusion. Histological analysis of the kidneys showed migration of polymorphonuclear leukocytes from the vascular bed to the interstitial tissue in the 60-min ischemic group after 24 h of reperfusion. We conclude that the duration of ischemia is critical for the development of damage

Urinary coagulation-fibrinolysis, kallirein-kinin systems and kininase in cases of preclampsia.

Science.gov (United States)

Mutoh, S; Kobayashi, M; Hirata, J; Itoh, N; Maki, M; Komatsu, Y; Yoshida, A; Sasa, H; Kuroda, K; Kikuchi, Y

1992-01-01

Urinary kallikrein and kallikrein activity significantly decreased in cases of preeclampsia (u-kall./CRE.index 42.39 +/- 9.66 ng/mg, u-kall. act./CRE.index 0.26 +/- 0.06 ng/min/mg), and urinary kininase II and kininase activity significantly increased (u-kininase/CRE.index 10.91 +/- 1.26 x 10(-3) IU/min/mg, u-kininase act./CRE.index 506.37 +/- 178.45 pg/min/mg) when compared with those of normal gravidas from 28 weeks to 42 weeks of gestation (u-kall./CRE.index 189.31 +/- 14.17 ng/mg, u-kall. act./CRE index 1.08 +/- 0.10 ng/min/mg, u-kininase/CRE.index 6.24 +/- 0.31 x 10(-3) IU/min/mg, u-kininase act./CRE.index 15.64 +/- 0.10 pg/min/mg). Urinary FPA, B beta 5-42, alpha 2-PI, and alpha 2PI-plasmin-complex (PIC) significantly increased in preeclampsia (u-FPA/CRE.index 23.59 +/- 8.47 ng/mg, u-B beta/CRE.index 105.26 +/- 29.30 ng/mg, u-alpha 2PI/CRE.index 121.53 +/- 43.57 ng/mg, u-PIC/CRE index 278.39 +/- 60.50 ng/mg) when compared with those of normal control group (u-FPA/CRE.index 0.92 +/- 0.04 ng/mg, u-B beta/CRE.index 12.15 +/- 0.44 ng/mg, u-alpha 2PI/CRE.index 4.18 +/- 0.33 ng/mg, u-PIC/CRE.index 5.98 +/- 1.15 ng/mg). Urinary urokinase markedly increased and urinary D-dimer was detected in severe cases of preeclampsia (u-UK/CRE.index 58.20 +/- 43.69 ng/mg, u-D-dimer 54.76 +/- 9.89 ng/ml) when compared with those of normal control group. These findings suggest that deficiency in urinary kinin excretion may induce hypertension in addition to the changes of urinary coagulation-fibrinolysis system that represents the occurrence of either the endothelial cell injury in the glomerulus or the renal tulbular damage in mild cases of preeclampsia, eventually resulting in the intra-renal vascular coagulation.

Code for plant identification (KKS) key in PC version. KKS-Schluessel-Programm in PC-Version

Energy Technology Data Exchange (ETDEWEB)

Pannenbaecker, K. (GABO Gesellschaft fuer Ablauforganisation und Informationsverarbeitung mbH, Erlangen (Germany) GABO Gesellschaft fuer Ablauforganisation und Informationsverarbeitung mbH, Muenchen (Germany))

1991-11-01

The plant identification system (KKS) as a common development of german plant operators, erection firms and also power plant oriented organisations have decisively influenced the technical-organizing activities of planning and erections as operations and maintenance of all kind of power plants. Fundamentals are three key parts, operation, armatures and function keys. Their management and application is executed by a plantidentification-key code in a PC version, which is briefly described in this report. (orig.).

Effects of kinins on glucose metabolism in vivo.

Science.gov (United States)

Hartl, W H; Jauch, K W; Wolfe, R R; Schildberg, F W

1990-01-01

Current concepts of the physiological importance of the kinin/prostaglandin system view these tissue factors as part of a defense system, which protects tissues from potentially noxious factors, such as hypoxia or destructive inflammatory reactions. This kinin-triggered defense reaction includes an improvement in cellular energy metabolism. The latter is brought about in peripheral tissues by an increased availability of glucose for anaerobic and aerobic glycolysis, whereas in liver tissue, energy-consuming reactions such as gluconeogenesis are attenuated. There is evidence that such favorable effects can also be produced in man when kinins are administered systemically. Prostaglandins are most likely the second messengers of kinin-induced metabolic effects. Thus, it may be advantageous to increase the availability of kinins either by exogenous infusion or by inhibiting endogenous degradation during postoperative stress or in diseases such as diabetes mellitus, in which glucose metabolism is severely disturbed.

Code for plant identification (KKS) key in PC version

International Nuclear Information System (INIS)

Pannenbaecker, K.

1991-01-01

The plant identification system (KKS) as a common development of german plant operators, erection firms and also power plant oriented organisations have decisively influenced the technical-organizing activities of planning and erections as operations and maintenance of all kind of power plants. Fundamentals are three key parts, operation, armatures and function keys. Their management and application is executed by a plantidentification-key code in a PC version, which is briefly described in this report. (orig.) [de

Kinin B1 Receptor Promotes Neurogenic Hypertension Through Activation of Centrally Mediated Mechanisms.

Science.gov (United States)

Sriramula, Srinivas; Lazartigues, Eric

2017-12-01

Hypertension is associated with increased activity of the kallikrein-kinin system. Kinin B1 receptor (B1R) activation leads to vasoconstriction and inflammation. Despite evidence supporting a role for the B1R in blood pressure regulation, the mechanisms by which B1R could alter autonomic function and participate in the pathogenesis of hypertension remain unidentified. We sought to explore whether B1R-mediated inflammation contributes to hypertension and investigate the molecular mechanisms involved. In this study, we tested the hypothesis that activation of B1R in the brain is involved in the pathogenesis of hypertension, using the deoxycorticosterone acetate-salt model of neurogenic hypertension in wild-type and B1R knockout mice. Deoxycorticosterone acetate-salt treatment in wild-type mice led to significant increases in B1R mRNA and protein levels and bradykinin levels, enhanced gene expression of carboxypeptidase N supporting an increase in the B1R ligand, associated with enhanced blood pressure, inflammation, sympathoexcitation, autonomic dysfunction, and impaired baroreflex sensitivity, whereas these changes were blunted or prevented in B1R knockout mice. B1R stimulation was further shown to involve activation of the ASK1-JNK-ERK1/2 and NF-κB pathways in the brain. To dismiss potential developmental alterations in knockout mice, we further used B1R blockade selectively in the brain of wild-type mice. Supporting the central origin of this mechanism, intracerebroventricular infusion of a specific B1R antagonist, attenuated the deoxycorticosterone acetate-salt-induced increase in blood pressure in wild-type mice. Our data provide the first evidence of a central role for B1R-mediated inflammatory pathways in the pathogenesis of deoxycorticosterone acetate-salt hypertension and offer novel insights into possible B1R-targeted therapies for the treatment of neurogenic hypertension. © 2017 American Heart Association, Inc.

Cathodic corrosion protection for the inside areas of metallic plants (KKS-I); Kathodischer Korrosionsschutz fuer die Innenflaechen von metallischen Anlagen (KKS-I)

Energy Technology Data Exchange (ETDEWEB)

Tenzer, Norbert [TZ-International Corrosion Consulting, Hagen (Germany)

2012-07-01

Cathodic corrosion protection for the inside areas of metallic plants (KKS-I) is a worldwide used technology in order to afford a safe protection of metallic plans against corrosion. This technology is used for plants in the treatment and storage of drinking water, for containers and reaction vessels in the chemical industry, for plants in the oil and gas industry as well as for containers and large-dimension pipelines containing seawater for the cooling of air liquefaction plants, power plants and seawater desalination plants, for examples. Furthermore, there exist further special applications for wastewater systems and biogas plants. The general description of the KKS-I shall supply the information to the operators of appropriate plants, that the cathodic corrosion protection also offers a wide range of applications for the protection of the inside areas of the plants against corrosion. Beside the previously mentioned standard areas of application there exist manifold further possibilities of application for metallic plants. It has to be emphasized that there are application possibilities not only for unalloyed or low alloy steels but also for stainless steels, aluminium, lead, copper, titanium and zinc. The regulation DIN EN 12499 firstly edited in 2003 contains the fundamentals, areas of application and specifications.

Radioimmunoassay of human urinary kallikrein

International Nuclear Information System (INIS)

Goering, W.

1980-01-01

Using a human urinary kallikrein, purified by means of Trasylol sepharose, it has been possible to develop a radioimmunoassay of kallikrein capable of detecting the substance down to a concentration of 0.5 ng/ml. The specific activity of the tracer labelled with 125-iodine using the Chloramine-T method was 30-70 nCi/ng of kallikrein. The antiserum titres for the antikallikrein serum were 1:20.000 up to 1:50.000. Human urine, submandibular and parotid salivae as well as pancreatic secretion in this RIA reacted in the same manner as the kallikrein standard solution. The kallikrein content in urine, as determined by the RIA was between 0 and 300 ng/ml, in the saliva between 400 and 2.000 ng/ml, and in the pancreatic juice between 300 and 12.000 ng/ml. Using human serum, only an incomplete immunological cross-reaction could be achieved. In human liquor as well as in animal preparation, no cross-reacting substances could be detected. (orig.) [de

Enhancement of lymphocyte proliferation by mouse glandular kallikrein.

Science.gov (United States)

Hu, Z Q; Murakami, K; Ikigai, H; Shimamura, T

1992-03-01

Mouse glandular kallikrein (mGK) strongly enhanced the spontaneous and mitogen-induced proliferation of lymphocytes. Both blast formation and 3H-TdR incorporation were dose-dependently enhanced at the same time many cells were killed. The enhancing activity was independent of EGF, because EGF-binding proteins (mGK-9 in mGK-6,9 mixture and mGK-13), renal kallikrein (mGK-6) and human kallikrein all displayed the same enhancement. A serine proteinase inhibitor, diisopropyl fluorophosphate, could block the enhancement by mGK. The new function suggests that mGK is important in the immune system as a regulatory molecule.

Crystallization and preliminary crystallographic studies of human kallikrein 7, a serine protease of the multigene kallikrein family

Energy Technology Data Exchange (ETDEWEB)

Fernández, Israel S. [Departamento de Ciencia de Proteínas, Centro de Investigaciones Biológicas-CSIC, Ramiro de Maeztu 9, 28040 Madrid (Spain); Ständker, Ludger [Departamento de Ciencia de Proteínas, Centro de Investigaciones Biológicas-CSIC, Ramiro de Maeztu 9, 28040 Madrid (Spain); Hannover Medical School, Center of Pharmacology, 30625 Hannover (Germany); Forssmann, Wolf-Georg [Hannover Medical School, Center of Pharmacology, 30625 Hannover (Germany); Giménez-Gallego, Guillermo; Romero, Antonio, E-mail: romero@cib.csic.es [Departamento de Ciencia de Proteínas, Centro de Investigaciones Biológicas-CSIC, Ramiro de Maeztu 9, 28040 Madrid (Spain)

2007-08-01

The cloning, expression, purification and crystallization of recombinant human kallikrein 7, directly synthesized in the active form in E. coli, is described. Diffraction data were collected to 2.8 Å resolution from native crystals. Human kallikreins are a group of serine proteases of high sequence homology whose genes are grouped as a single cluster at chromosome 19. Although the physiological roles of kallikreins are generally still unknown, members of the kallikrein family have been clearly implicated in pathological situations such as cancer and psoriasis. Human kallikrein 7 (hK7) has been shown to be involved in pathological keratinization, psoriasis and ovarian cancer. In order to gain insight into the molecular structure of this protein, hK7 was crystallized after recombinant production in its folded and active form using a periplasmic secretion vector in Escherichia coli. The crystals belonged to the rhombohedral space group H32 and diffracted to 2.8 Å. The phase problem was solved by molecular replacement using the mouse kallikrein-related protein neuropsin. Completion of the model and structure refinement are under way.

A model of objects based on KKS for the processing of alarms at the Angra 2 nuclear power plant; Um modelo de objetos baseado em KKS para o processamento de alarmes da usina nuclear de Angra 2

Energy Technology Data Exchange (ETDEWEB)

Silva, Paulo Adriano da

2000-03-01

The purpose of this work is to present a new model of the alarm annunciation system of the Angra 2 nuclear power plant, using concepts of object based modeling and having as basic the Angra 2 Systems and Components Identification System - KKS. The present structure of the Computerized Alarm System - CAS of Angra 2 does not permit a fast visualization of the incoming alarms in case that a great number of them go off, because the monitors can only show 7 indications at a time. The herein proposed model permits a fast identification of the generated alarms, making possible for the operator to have a general view of the current nuclear power plant status. Its managing tree structure has an hierarchical dependence among its nodes, from where, the presently activated alarms are shown. Its man-machine interface is easy interaction and understand because it is based on structure well known by the Angra 2 operators which is the Angra 2 Systems and Components Identification System - KKS. The project was implemented in the format of an Angra 2 Alarms Supervision System (SSAA), and, for purpose of simulation, 5 system of the Angra 2 Nuclear Power Plant have been chosen. The data used in the project like measurement KKS, measurement limits, unity, setpoints, alarms text and systems flow diagrams, are actual data of the Angra 2 Nuclear Power Plant. The Visual Basic programming Language has been used, with emphasis to the object oriented programming, which and modification, without modifying the program code. Event hough using the Visual Basic for programming, the model has shown, for its purpose, a satisfactory real time execution. (author)

Administration of angiotensin II and a bradykinin B2 receptor blocker in midpregnancy impairs gestational outcome in guinea pigs.

Science.gov (United States)

Valdés, Gloria; Schneider, Daniela; Corthorn, Jenny; Ortíz, Rita; Acuña, Stephanie; Padilla, Oslando

2014-06-04

The opposing renin-angiotensin system (RAS) and kallikrein-kinin system (KKS) are upregulated in pregnancy and localize in the utero-placental unit. To test their participation as counter-regulators, circulating angiotensin II (AII) was exogenously elevated and the bradykinin B2 receptor (B2R) was antagonized in pregnant guinea-pigs. We hypothesized that disrupting the RAS/KKS balance during the period of maximal trophoblast invasion and placental development would provoke increased blood pressure, defective trophoblast invasion and a preeclampsia-like syndrome. Pregnant guinea-pigs received subcutaneous infusions of AII (200 μg/kg/day), the B2R antagonist Bradyzide (BDZ; 62.5 microg/kg/day), or both (AII + BDZ) from gestational day 20 to 34. Non-pregnant cycling animals were included in a control group (C NP) or received AII + BDZ (AII + BDZ NP) during 14 days. Systolic blood pressure was determined during cycle in C NP, and on the last day of infusion, and 6 and 26 days thereafter in the remaining groups. Twenty six days after the infusions blood and urine were extracted, fetuses, placentas and kidneys were weighed, and trophoblast invasion of spiral arteries was defined in the utero-placental units by immunocytochemistry. Systolic blood pressure transiently rose in a subgroup of the pregnant females while receiving AII + BDZ infusion, but not in AII + BDZ NP. Plasma creatinine was higher in AII- and BDZ-treated dams, but no proteinuria or hyperuricemia were observed. Kidney weight increased in AII + BDZ-treated pregnant and non-pregnant females. Aborted and dead fetuses were increased in dams that received AII and AII + BDZ. The fetal/placental weight ratio was reduced in litters of AII + BDZ-treated mothers. All groups that received interventions during pregnancy showed reduced replacement of endothelial cells by extravillous trophoblasts in lateral and myometrial spiral arteries. The acute effects on fetal viability, and the persistently impaired renal

Unveiling the participation of avian kinin ornithokinin and its receptors in the chicken inflammatory response.

Science.gov (United States)

Guabiraba, Rodrigo; Garrido, Damien; Bailleul, Geoffrey; Trotereau, Angélina; Pinaud, Mélanie; Lalmanach, Anne-Christine; Chanteloup, Nathalie K; Schouler, Catherine

2017-06-01

Vasoactive peptides are key early mediators of inflammation released through activation of different enzymatic systems. The mammalian kinin-kallikrein (K-KLK) system produces bradykinin (BK) through proteolytic cleavage of a kininogen precursor by enzymes named kallikreins. BK acts through specific ubiquitous G-protein coupled receptors (B1R and B2R) to participate in physiological processes and inflammatory responses, such as activation of mononuclear phagocytes. In chickens, the BK-like nonapeptide ornithokinin (OK) has been shown to promote intracellular calcium increase in embryonic fibroblasts and to be vasodilatory in vivo. Also, one of its receptors (B2R) was already cloned. However, the participation of chicken K-KLK system components in the inflammatory response remains unknown and was therefore investigated. We first showed that B1R, B2R and kininogen 1 (KNG1) are expressed in unstimulated chicken tissues and macrophages. We next showed that chicken B1R and B2R are expressed at transcript and protein levels in chicken macrophages and are upregulated by E. coli LPS or avian pathogenic E. coli (APEC) infection. Interestingly, exogenous OK induced internalization and degradation of OK receptors protein, notably B2R. Also, OK induced intracellular calcium increase and potentiated zymosan-induced ROS production and Dextran-FITC endocytosis by chicken macrophages. Exogenous OK itself did not promote APEC killing and had no pro-inflammatory effect. However, when combined with LPS or APEC, OK upregulated cytokine/chemokine gene expression and NO production by chicken macrophages. This effect was not blocked by canonical non-peptide B1R or B2R receptor antagonists but was GPCR- and PI3K/Akt-dependent. In vivo, pulmonary colibacillosis led to upregulation of OK receptors expression in chicken lungs and liver. Also, colibacillosis led to significant upregulation of OK precursor KNG1 expression in liver and in cultured hepatocytes (LMH). We therefore provide hitherto

Development of a radioimmunoassay for pig pancreatic kallikrein

Energy Technology Data Exchange (ETDEWEB)

Fink, E; Guettel, C [Muenchen Univ. (Germany, F.R.). Chirurgische Klinik

1978-07-01

A radioimmunoassay for the determination of pig pancreatic kallikrein was developed. The chloramine-T method was employed for the labelling of the antigen with /sup 125/I. The assay allows the determination of kallikrein in concentrations as low as 0.4 ..mu..g/l. Pig urinary and pig submandibular kallikreins are indistinguishable from pig pancreatic kallikrein by the assay. No cross reactivity was observed for bovine trypsin and chymotrypsin, porcine trypsin and kallikreins of guinea pig submandibular glands and guinea pig coagulation glands. Because of the high specificity of the assay, which is not attainable with conventional assays based on the enzymatic activity, the radioimmunoassay is highly suited for investigations into the physiological role and the pharmacological mechanism of action of pig glandular kallikreins.

Measurements of urinary kinins by HPLC-radioimmunoassay

International Nuclear Information System (INIS)

Fejes-Toth, G.; Naray-Fejes-Toth, A.; Froelich, J.C.

1984-01-01

In this paper the authors describe a method for the individual determination of urinary kinins. Extraction from the urine is performed on an Amberlite CG-50 column and kinins are eluted with formic acid. The samples are further purified and kinins are separated by reversed phase HPLC. Bradykinin and lysylbradykinin are quantified by a sensitive radioimmunoassay capable of detecting 0.1 fmol of either peptide. Procedural losses are monitored by measuring the recovery of [ 3 H]bradykinin and [ 3 H]lysylbradykinin. Simple methods for labeling of bradykinin and lysylbradykinin with tritium are also presented. Recoveries of [ 3 H]bradykinin and [ 3 H]lysylbradykinin from biological material ranged between 77 and 91%. The combination of HPLC with radioimmunoassay makes it possible to determine kinin concentrations of biological samples with a higher sensitivity and greater specificity than previous methods. (Auth.)

Selection of Protease Inhibitors to Prevent or Attenuate Inflammatory Processes

Science.gov (United States)

2007-08-01

because of this, the generic name of the bee-eater was chosen as the name of the database. In Greek mythology . Merops was a Trojan seer who was father...20031. Given the protective B,-receptor mediated actions in the cardiovascular and renal systems and because a large body of animal data suggests...More inhibitors for plasma kallikrein are discussed in Paragraph 5.5. The use of mice or rats as animal models for studying the kallikrein-kinin

The angiotensin II type 1 receptor antagonist Losartan binds and activates bradykinin B2 receptor signaling

DEFF Research Database (Denmark)

Bonde, Marie Mi; Olsen, Kristine Boisen; Erikstrup, Niels

2011-01-01

The angiotensin II type 1 receptor (AT1R) blocker (ARB) Losartan has cardioprotective effects during ischemia-reperfusion injury and inhibits reperfusion arrhythmias -effects that go beyond the benefits of lowering blood pressure. The renin-angiotensin and kallikrein-kinin systems are intricately...

Calibrated kallikrein generation in human plasma

DEFF Research Database (Denmark)

Biltoft, D; Sidelmann, J J; Olsen, L F

2016-01-01

generation method as a template. RESULTS: A suitable kallikrein specific fluorogenic substrate was identified (KM=0.91mM, kcat=19s(-1)), and kallikrein generation could be measured in undiluted plasma when silica was added as activator. Disturbing effects, including substrate depletion and the inner......-filter effect, however, affected the signal. These problems were corrected for by external calibration with α2-macroglobulin-kallikrein complexes. Selectivity studies of the substrate, experiments with FXII and PK depleted plasmas, and plasma with high or low complement C1-esterase inhibitor activity indicated...

Structure and chromosomal localization of the human renal kallikrein gene

International Nuclear Information System (INIS)

Evans, B.A.; Yun, Z.X.; Close, J.A.

1988-01-01

Glandular kallikreins are a family of proteases encoded by a variable number of genes in different mammalian species. In all species examined, however, one particular kallikrein is functionally conserved in its capacity to release the vasoactive peptide, Lys-bradykinin, from low molecular weight kininogen. This kallikrein is found in the kidney, pancreas, and salivary gland, showing a unique pattern of tissue-specific expression relative to other members of the family. The authors have isolated a genomic clone carrying the human renal kallikrein gene and compared the nucleotide sequence of its promoter region with those of the mouse renal kallikrein gene and another mouse kallikrein gene expressed in a distinct cell type. They find four sequence elements conserved between renal kallikrein genes from the two species. They have also shown that the human gene is localized to 19q13, a position analogous to that of the kallikrein gene family on mouse chromosome 7

A model of objects based on KKS for the processing of alarms at the Angra 2 nuclear power plant

International Nuclear Information System (INIS)

Silva, Paulo Adriano da

2000-03-01

The purpose of this work is to present a new model of the alarm annunciation system of the Angra 2 nuclear power plant, using concepts of object based modeling and having as basic the Angra 2 Systems and Components Identification System - KKS. The present structure of the Computerized Alarm System - CAS of Angra 2 does not permit a fast visualization of the incoming alarms in case that a great number of them go off, because the monitors can only show 7 indications at a time. The herein proposed model permits a fast identification of the generated alarms, making possible for the operator to have a general view of the current nuclear power plant status. Its managing tree structure has an hierarchical dependence among its nodes, from where, the presently activated alarms are shown. Its man-machine interface is easy interaction and understand because it is based on structure well known by the Angra 2 operators which is the Angra 2 Systems and Components Identification System - KKS. The project was implemented in the format of an Angra 2 Alarms Supervision System (SSAA), and, for purpose of simulation, 5 system of the Angra 2 Nuclear Power Plant have been chosen. The data used in the project like measurement KKS, measurement limits, unity, setpoints, alarms text and systems flow diagrams, are actual data of the Angra 2 Nuclear Power Plant. The Visual Basic programming Language has been used, with emphasis to the object oriented programming, which and modification, without modifying the program code. Event hough using the Visual Basic for programming, the model has shown, for its purpose, a satisfactory real time execution. (author)

Renal Kallikrein Activation and Renoprotection after Dual Blockade of Renin-Angiotensin System in Diet-Induced Diabetic Nephropathy

Directory of Open Access Journals (Sweden)

Xia Zou

2015-01-01

Full Text Available Purpose. The objective of this study is to investigate the effect of dual blockage of renin-angiotensin system (RAS on renal kallikrein expression and inflammatory response in diabetic nephropathy (DN. Methods. Rats were randomly divided into 5 groups with 10 rats in each group: normal control; DN model induced by high fat and high sucrose diets; and DN treated with either benazepril 10 mg/kg/d, irbesartan 30 mg/kg/d, or both. After 8-week treatment, we examined changes in the kidney histopathology, function and immunohistochemical stain of kallikrein, macrophage marker CD68, and profibrotic markers transforming growth factor- (TGF- β and α-smooth muscle action (SMA. Results. DN rats showed enlarged kidneys with glomerulosclerosis, interstitial chronic inflammation and fibrosis, and proteinuria. All the pathological damage and functional impairments were improved after the RAS blockades (all P<0.05. Compared with monotherapy, combined treatment further alleviated the kidney impairments in parallel to increased tubular immunoreactivity for kallikrein and decreased immunopositive cells for CD68, TGF-β, and α-SMA. Conclusion. The renoprotective effects of the dual RAS blockade in diabetic nephropathy may be attributed to improved tubular kallikrein expression and interstitial inflammatory response.

Nuclei of dwarf spheroidal galaxies KKs 3 and ESO 269-66 and their counterparts in our Galaxy

Science.gov (United States)

Sharina, M. E.; Shimansky, V. V.; Kniazev, A. Y.

2017-10-01

We present the analysis of medium-resolution spectra obtained at the Southern African Large Telescope for nuclear globular clusters (GCs) in two dwarf spheroidal galaxies (dSphs). The galaxies have similar star formation histories, but they are situated in completely different environments. ESO 269-66 is a close neighbour of the giant S0 NGC 5128. KKs 3 is one of the few truly isolated dSphs within 10 Mpc. We estimate the helium abundance Y = 0.3, age = 12.6 ± 1 Gyr, [Fe/H] = -1.5, -1.55 ± 0.2 dex, and abundances of C, N, Mg, Ca, Ti, and Cr for the nuclei of ESO 269-66 and KKs 3. Our surface photometry results using Hubble Space Telescope images yield the half-light radius of the cluster in KKs 3, rh = 4.8 ± 0.2 pc. We demonstrate the similarities of medium-resolution spectra, ages, chemical compositions, and structure for GCs in ESO 269-66 and KKs 3 and for several massive Galactic GCs with [Fe/H] ∼ -1.6 dex. All Galactic GCs posses Extended Blue Horizontal Branches and multiple stellar populations. Five of the selected Galactic objects are iron-complex GCs. Our results indicate that the sample GCs observed now in different environments had similar conditions of their formation ∼1 Gyr after the Big Bang.

Impact of angiotensin and endothelin converting enzymes and related bradykinin on renal functions in L-NAME hypertensive rats

Science.gov (United States)

Omar, Ali Zainal; Maulood, Ismail M.

2017-09-01

The renin-angiotensin system (RAS), one of the most important hormonal systems, controls the kidney functions by regulating fluid volume, and electrolyte balance. The current study included the effects of kinin-kallikrein system (KKS) and its interaction with both angiotensin converting enzyme (ACE) and endothelin converting enzyme (ECE) on some of kidney function test parameters. In the present experiment, rats were divided into six groups, the first group was infused with normal saline, the second group was L-NG-Nitroarginine methyl ester (L-NAME) treated rats, third group was bradykinin (BK), forth group was captopril (ACEi), fifth group was phosphoramidon (ECEi), sixth group was a combination of BK with phosphoramidon. L-NAME was intravenously infused for one hour to develop systematic hypertension in male rats. After one hour of infusion, the results showed that L-NAME significantly increased serum creatinine. While, it decreased glomerular filtration rate (GFR), and K+ excretion rate. Moreover, BK increased packed cell volume PCV%, serum creatinine and K+ ion concentration. While, it reduced GFR, serum Ca+2 ion concentration, K+ and Na+ excretion rates. On the other hand, captopril infusion showed its effect by reduction in GFR, serum Ca+2 ion and electrolyte excretion rates. Phosphoramidon an ECEi dramatically reduced serum Ca+2 ion, but it increased pH, GFR and Ca+2 excretion rate. The results suggested that BK and Captopril each alone severely reduces GFR value. Interestingly, inhibition of ET-1 production via phosphoramidon could markedly elevate GFR values.

Production of cellulase and xylanase in a bubble gum column using immobilized Aspergillus niger KKS

Energy Technology Data Exchange (ETDEWEB)

Kang, Seong-Woo; Kim, Seung-Woo [Univ. of Suwon (Korea, Republic of); Lee, Jin-Suk [Korea Institute of Energy Research, Daejeon (Korea, Republic of)

1995-05-01

Aspergillus niger KKS, isolated from a farmland near Suwon, was immobilized on Celite and polyurethane foams. Enzyme activities produced by the immobilized cell system in a bubble column were higher than that of shake-flask culture. The enzyme productivities were twice as high. {Beta}-Glucosidase, {Beta}-xylosidase, and xylanase activities obtained in a bubble column were significant when the ground rice straw was used as a substrate. 9 refs., 2 figs., 3 tabs.

New power plant terminology (KKS) from the view of information psychology and ergonomics

Energy Technology Data Exchange (ETDEWEB)

Bohr, E; Becker, G; Wildberg, D

1982-01-01

The operating staff of power plants have to deal daily with coded designations of devices and plants. Two factors determine the simple and reliable compilation, processing and reproduction of such designations: first, the formal-logical and technological consistency of the terminological system, and secondly, its compatibility with the human faculties of taking in and processing alphanumerically coded information. The KKS is investigated from both points of view and the problems of its structure and its utilization by human beings are pointed out. Some requirements to a logically consistent terminological system which is closely related to the technical way of thinking and talking and to practical usage result from this analysis.

Excess antibody immunoassays for rat glandular kallikreins. Measurement of kallikrein from different organs in the presence of cross-reacting antigens

International Nuclear Information System (INIS)

Johansen, L.; Oerstavik, T.B.; Holck, M.; Nustad, K.

1983-01-01

An immunoradiometric assay has previously been developed for measurement of rat glandular kallikrein. In the present paper, further studies on the specificity and sensitivity of the method are described. Problems of interference of immunologically cross-reacting antigens were overcome by proper preabsorption of the antibody. A method was thus established in which enzymatic activity of the immunoreactive kallikrein could be measured even in the presence of enzymes sharing immunological determinants and substrate specificity with kallikrein. Two variants of the immunoradiometric assay have been evaluated. A simplified version with simultaneous addition of all reagents gave results equal to those obtained in the original assay. A further modification with delayed addition of the solid-phase antibody, gave considerable improvement in assay sensitivity. (Auth.)

Expression of kallikrein-related peptidase 7 is decreased in prostate cancer

Directory of Open Access Journals (Sweden)

Chong-Yu Zhang

2015-02-01

Full Text Available Recent evidence suggests that the human kallikrein 7 (KLK7 is differentially regulated in a variety of tumors. The aim of this study was to determine the expression of kallikrein-related peptidase 7 and KLK7 in our large collection of prostate samples. Between August 2000 and December 2012, 116 patients with histologically confirmed prostate cancer (PCa and 92 with benign prostate hyperplasia (BPH were recruited into the study. Using immunohistochemistry, quantitative reverse transcription polymerase chain reaction (RT-PCR and western blot, kallikrein-related peptidase 7 expression in BPH and PCa tissues was determined at the mRNA and protein levels. The relationships between kallikrein-related peptidase 7 mRNA expression and clinicopathological features were analyzed. A total of 64 of 92 (69.57% benign cases showed positive staining for KLK7 and 23 of 116 (19.83% malignant cases showed positive, the difference of KLK7 expression between PCa and BPH was statistically significant (P < 0.001. The expression level of kallikrein-related peptidase 7 mRNA was significantly decreased in PCa tissues compared with that in BPH tissues and normal prostate tissue. Kallikrein-related peptidase 7 mRNA exhibited different expression patterns in terms of localization depending on pathological category of PCa. Similarly, our western immunoblot analyses demonstrated that the protein expression levels of KLK7 was lower in PCa than in BPH tissues and normal prostate tissue. Kallikrein-related peptidase 7 and KLK7 expression are down-regulated in PCa and lower expression of kallikrein-related peptidase 7 closely correlates with higher Gleason score and higher prostate-specific antigen level.

Kininogen Cleavage Assay: Diagnostic Assistance for Kinin-Mediated Angioedema Conditions.

Directory of Open Access Journals (Sweden)

Rémi Baroso

Full Text Available Angioedema without wheals (AE is a symptom characterised by localised episodes of oedema presumably caused by kinin release from kininogen cleavage. It can result from a hereditary deficiency in C1 Inhibitor (C1Inh, but it can present with normal level of C1Inh. These forms are typically difficult to diagnose although enhanced kinin production is suspected or demonstrated in some cases.We wanted to investigate bradykinin overproduction in all AE condition with normal C1Inh, excluding cases with enhanced kinin catabolism, and to propose this parameter as a disease biomarker.We retrospectively investigated high molecular weight kininogen (HK cleavage pattern, using gel electrophoresis and immunorevelation. Plasma samples were drawn using the same standardised procedure from blood donors or AE patients with normal C1Inh conditions, normal kinin catabolism, and without prophylaxis.Circulating native HK plasma concentrations were similar in the healthy men (interquartile range: 98-175μg/mL, n = 51 and in healthy women (90-176μg/mL, n = 74, while HK cleavage was lower (p14.4% HK cleavage for men; 33.0% HK cleavage for women, with >98% specificity achieved for all parameters. In plasma from patients undergoing recovery two months after oestrogen/progestin combination withdrawal (n = 13 or two weeks after AE attack (n = 2, HK cleavage was not fully restored, suggesting its use as a post-attack assay.As a diagnostic tool, HK cleavage can offer physicians supportive arguments for kinin production in suspected AE cases and improve patient follow-up in clinical trials or prophylactic management.

Development of a radioimmunoassay for pig pancreatic kallikrein and its application in physiological studies

International Nuclear Information System (INIS)

Fink, E.; Guettel, C.; Seifert, J.

1978-01-01

A RIA for pig pancreatic kallikrein has been developed. Purified kallikrein was labelled with 125 I. The use of radioimmunoassays in investigating the intestinal absorption of pig pancreas kallikrein is dealt with. (VJ) [de

Effect of 3-arylamino-1,2-dihydro-3H-1,4-benzodiazepine-2-ones on the bradykinin-induced smooth muscle contraction

Directory of Open Access Journals (Sweden)

P. A. Virych

2017-01-01

Full Text Available Damage to tissue, inflammation and disruption of normal functioning of organs are often accompanied by pain. In pain perceptions, the kinin-kallikrein system with bradykinin as mediator is very important. Regulatory activity of the kinin-kallikrein system permits the control of inflammation, pain, vascular tone and other functions. A new group of substances that may used for this purpose are 3-substituted 1,4-benzdiazepinones. We analyzed the effect of 3-aryl amino-1,2-dihydro-3H-1,4-benzodiazepine-2-ones derivatives on the normalized maximal rate of bradykinin-induced smooth muscle contraction of the stomach in the presence of calcium channel blockers verapamil (1 μM and gadolinium (300 μM. The levels of bradykinin and 3-arylamino-1,2-dihydro-3H-1,4-benzodiazepine-2-ones in the incubation solution were 10–6 M. Data processing on the dynamics of contraction was performed according to the method of T. Burdyha and S. Kosterin. Statistically significant changes were found for MX-1828. This compound reduced the maximal normalized rate of bradykinin-induced smooth muscle contraction in the presence of Gd3+ and verapamil by 19.3% and 32.0%, respectively. Also, MX-1828 demonstrated effects similar to those of the competitive inhibitor bradykinin B2-receptor – des-Arg9-bradykinin-acetate, which is possible evidence of its interaction with the receptor or signal transduction pathways. MX-1828 additionally reduced the maximum normalized rate of relaxation by 6.2% in the presence of Gd3+. This effect was demonstrated for MX-1906 in the presence of verapamil with additional reduction of the maximal normalized rate of relaxation, which was 26.4%. The results suggest the presence of inhibitory interaction between MX-1828 and kinin-kallikrein system receptors or signal transduction pathways. The effects which were found for MX-1906 require further studies to clarify the mechanisms of influence on bradykinin-induced smooth muscle contraction.

Laser Ignition Microthruster Experiments on KKS-1

Science.gov (United States)

Nakano, Masakatsu; Koizumi, Hiroyuki; Watanabe, Masashi; Arakawa, Yoshihiro

A laser ignition microthruster has been developed for microsatellites. Thruster performances such as impulse and ignition probability were measured, using boron potassium nitrate (B/KNO3) solid propellant ignited by a 1 W CW laser diode. The measured impulses were 60 mNs ± 15 mNs with almost 100 % ignition probability. The effect of the mixture ratios of B/KNO3 on thruster performance was also investigated, and it was shown that mixture ratios between B/KNO3/binder = 28/70/2 and 38/60/2 exhibited both high ignition probability and high impulse. Laser ignition thrusters designed and fabricated based on these data became the first non-conventional microthrusters on the Kouku Kousen Satellite No. 1 (KKS-1) microsatellite that was launched by a H2A rocket as one of six piggyback satellites in January 2009.

Microvesicle transfer of kinin B1-receptors is a novel inflammatory mechanism in vasculitis.

Science.gov (United States)

Kahn, Robin; Mossberg, Maria; Ståhl, Anne-Lie; Johansson, Karl; Lopatko Lindman, Ingrid; Heijl, Caroline; Segelmark, Mårten; Mörgelin, Matthias; Leeb-Lundberg, L M Fredrik; Karpman, Diana

2017-01-01

During vasculitis, activation of the kinin system induces inflammation, whereby the kinin B1-receptor is expressed and activated after ligand binding. Additionally, activated blood cells release microvesicles into the circulation. Here we determined whether leukocyte-derived microvesicles bear B1-kinin receptors during vasculitis, and if microvesicles transfer functional B1-receptors to recipient cells, thus promoting inflammation. By flow cytometry, plasma from patients with vasculitis were found to contain high levels of leukocyte-derived microvesicles bearing B1-receptors. Importantly, renal biopsies from two patients with vasculitis showed leukocyte-derived microvesicles bearing B1-receptors docking on glomerular endothelial cells providing in vivo relevance. Microvesicles derived from B1-receptor-transfected human embryonic kidney cells transferred B1-receptors to wild-type human embryonic kidney cells, lacking the receptor, and to glomerular endothelial cells. The transferred B1-receptors induced calcium influx after B1-receptor agonist stimulation: a response abrogated by a specific B1-receptor antagonist. Microvesicles derived from neutrophils also transferred B1-receptors to wild-type human embryonic kidney cells and induced calcium influx after stimulation. Thus, we found a novel mechanism by which microvesicles transfer functional receptors and promote kinin-associated inflammation. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Nicotine impairs cyclooxygenase-2-dependent kinin-receptor-mediated murine airway relaxations

International Nuclear Information System (INIS)

Xu, Yuan; Cardell, Lars-Olaf

2014-01-01

Introduction: Cigarette smoke induces local inflammation and airway hyperreactivity. In asthmatics, it worsens the symptoms and increases the risk for exacerbation. The present study investigates the effects of nicotine on airway relaxations in isolated murine tracheal segments. Methods: Segments were cultured for 24 h in the presence of vehicle, nicotine (10 μM) and/or dexamethasone (1 μM). Airway relaxations were assessed in myographs after pre-contraction with carbachol (1 μM). Kinin receptors, cyclooxygenase (COX) and inflammatory mediator expressions were assessed by real-time PCR and confocal-microscopy-based immunohistochemistry. Results: The organ culture procedure markedly increased bradykinin- (selective B 2 receptor agonist) and des-Arg 9 -bradykinin- (selective B 1 receptor agonist) induced relaxations, and slightly increased relaxation induced by isoprenaline, but not that induced by PGE 2 . The kinin receptor mediated relaxations were epithelium-, COX-2- and EP2-receptor-dependent and accompanied by drastically enhanced mRNA levels of kinin receptors, as well as inflammatory mediators MCP-1 and iNOS. Increase in COX-2 and mPGES-1 was verified both at mRNA and protein levels. Nicotine selectively suppressed the organ-culture-enhanced relaxations induced by des-Arg 9 -bradykinin and bradykinin, at the same time reducing mPGES-1 mRNA and protein expressions. α7-nicotinic acetylcholine receptor inhibitors α-bungarotoxin and MG624 both blocked the nicotine effects on kinin B 2 receptors, but not those on B 1 . Dexamethasone completely abolished kinin-induced relaxations. Conclusion: It is tempting to conclude that a local inflammatory process per se could have a bronchoprotective component by increasing COX-2 mediated airway relaxations and that nicotine could impede this safety mechanism. Dexamethasone further reduced airway inflammation together with relaxations. This might contribute to the steroid resistance seen in some patients with asthma

Nicotine impairs cyclooxygenase-2-dependent kinin-receptor-mediated murine airway relaxations

Energy Technology Data Exchange (ETDEWEB)

Xu, Yuan, E-mail: yuan.xu@ki.se; Cardell, Lars-Olaf

2014-02-15

Introduction: Cigarette smoke induces local inflammation and airway hyperreactivity. In asthmatics, it worsens the symptoms and increases the risk for exacerbation. The present study investigates the effects of nicotine on airway relaxations in isolated murine tracheal segments. Methods: Segments were cultured for 24 h in the presence of vehicle, nicotine (10 μM) and/or dexamethasone (1 μM). Airway relaxations were assessed in myographs after pre-contraction with carbachol (1 μM). Kinin receptors, cyclooxygenase (COX) and inflammatory mediator expressions were assessed by real-time PCR and confocal-microscopy-based immunohistochemistry. Results: The organ culture procedure markedly increased bradykinin- (selective B{sub 2} receptor agonist) and des-Arg{sup 9}-bradykinin- (selective B{sub 1} receptor agonist) induced relaxations, and slightly increased relaxation induced by isoprenaline, but not that induced by PGE{sub 2}. The kinin receptor mediated relaxations were epithelium-, COX-2- and EP2-receptor-dependent and accompanied by drastically enhanced mRNA levels of kinin receptors, as well as inflammatory mediators MCP-1 and iNOS. Increase in COX-2 and mPGES-1 was verified both at mRNA and protein levels. Nicotine selectively suppressed the organ-culture-enhanced relaxations induced by des-Arg{sup 9}-bradykinin and bradykinin, at the same time reducing mPGES-1 mRNA and protein expressions. α7-nicotinic acetylcholine receptor inhibitors α-bungarotoxin and MG624 both blocked the nicotine effects on kinin B{sub 2} receptors, but not those on B{sub 1}. Dexamethasone completely abolished kinin-induced relaxations. Conclusion: It is tempting to conclude that a local inflammatory process per se could have a bronchoprotective component by increasing COX-2 mediated airway relaxations and that nicotine could impede this safety mechanism. Dexamethasone further reduced airway inflammation together with relaxations. This might contribute to the steroid resistance seen in

The Long-Term Outcome Comparison of Different Time-Delayed Kallikrein Treatments in a Mouse Cerebral Ischemic Model

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Yaohui Ni

2018-01-01

Full Text Available Delayed administration of kallikrein after cerebral infarction can improve neurological function. However, the appropriate kallkrein treatment time after ischemic stroke has not been illuminated. In this study, we compared the long-term outcome among three kallikrein therapeutic regimens starting at different time points following mouse cerebral ischemia. Furthermore, the protective mechanisms involving neurogenesis, angiogenesis, and AKT-GSK3β-VEGF signaling pathway were analyzed. Human tissue kallikrein was injected through the tail vein daily starting at 8 h, 24 h, or 36 h after right middle cerebral artery occlusion (MCAO until the 28th day. Three therapeutic regimens all protected against neurological dysfunction, but kallikrein treatment starting at 8 h after MCAO had the best efficacy. Additionally, kallikrein treatment at 8 h after MCAO significantly enhanced cell proliferation including neural stem cell and induced differentiation of neural stem cell into mature neuron. Kallikrein treatment starting at 8 h also promoted more angiogenesis than other two treatment regimens, which was associated with AKT-GSK3β-VEGF signaling pathway. Thus, we confirm that three delayed kallikrein treatments provide protection against cerebral infarction and furthermore suggest that kallikrein treatment starting at 8 h had a better effect than that at 24 h and 36 h. These findings provide the experimental data contributing to better clinical application of exogenous kallikrein.

Activation of Membrane-Bound Kallikrein and Renin in the Kidney.

Science.gov (United States)

1980-05-23

included repeated washings with hypotonic buffer. Kallikrein activity in the PM fraction (PM-kallikrein) averaged 1.81 nmol of S-2266 hydrolyzed per min...thousand Fig. 1 times more active than lysolecithin on a molar basis. Lecithin and arachidonic acid were active only at a much higher concentration...taglandin E2 (11), arachidonic acid or lecithin . However, melittin, on a molar basis, was about three orders of magnitude more potent than

The single kinin receptor signals to separate and independent physiological pathways in Malpighian tubules of the yellow fever mosquito

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In the past we have used the leucokinins, the kinins of the cockroach Leucophaea, to evaluate the mechanism of diuretic action of kinin peptides in Malpighian tubules of the yellow fever mosquito Aedes aegypti. Now using aedeskinins, the kinins of Aedes, are available, we find that in isolated Aede...

Effect of focal irradiation on plasma kallikrein activity in tumor bearing rats

International Nuclear Information System (INIS)

Makoyo, P.O.Z.R.; West, W.L.

1977-01-01

The activated plasma kallikrein from tumor bearing rats before and after focal irradiation of the hind limbs was measured by the hydrolysis of 0.015M N-(p-toluene sulfonyl)-L arginine methyl ester (TAME). Blood was collected from abdominal aorta of rats anesthetized with diethyl ether into plastic tubes containing 1 volume of 3.8 percent sodium citrate for each 9 volumes. Plasma was isolated by centrifugation (2000 g) at 4 0 C. Small pieces of minced tumor tissue were inserted in a trochar and inoculated in the hind limbs of the rats. Morris hepatomas 7777 and 3924A were transplanted subcutaneously over the hind legs while Walker 256 tumor was transplanted intramuscularly in the hind limbs. Plasma kallikrein (μm TAME utilized/ml/hr) was decreased in three different groups of tumor bearing rats: Walker tumor from 207 +- 34 to 114 +- 30 Hepatoma 7777 from 219 +- 13 to 106 +- 3 and Hepatoma 3924A from 227 +- 7 to 133 +- 5. Two hours after focal irradiation (1000 R) plasma kallikrein decreased further in Walker tumor and hepatoma 7777 to 55 +- 5 and 96 +- 3.6 respectively. The plasma of tumor bearing rats becomes deficient in kallikrein at about the time metastases may be identified. The acute fall in plasma kallikrein is consistent with the overall stress mechanism

Activation of the kinin B1 receptor attenuates melanoma tumor growth and metastasis.

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Patricia Dillenburg-Pilla

Full Text Available Melanoma is a very aggressive tumor that does not respond well to standard therapeutic approaches, such as radio- and chemotherapies. Furthermore, acquiring the ability to metastasize in melanoma and many other tumor types is directly related to incurable disease. The B1 kinin receptor participates in a variety of cancer-related pathophysiological events, such as inflammation and angiogenesis. Therefore, we investigated whether this G protein-coupled receptor plays a role in tumor progression. We used a murine melanoma cell line that expresses the kinin B1 receptor and does not express the kinin B2 receptor to investigate the precise contribution of activation of the B1 receptor in tumor progression and correlated events using various in vitro and in vivo approaches. Activation of the kinin B1 receptor in the absence of B2 receptor inhibits cell migration in vitro and decreases tumor formation in vivo. Moreover, tumors formed from cells stimulated with B1-specific agonist showed several features of decreased aggressiveness, such as smaller size and infiltration of inflammatory cells within the tumor area, higher levels of pro-inflammatory cytokines implicated in the host anti-tumor immune response, lower number of cells undergoing mitosis, a poorer vascular network, no signs of invasion of surrounding tissues or metastasis and increased animal survival. Our findings reveal that activation of the kinin B1 receptor has a host protective role during murine melanoma tumor progression, suggesting that the B1 receptor could be a new anti-tumor GPCR and provide new opportunities for therapeutic targeting.

Prognostic significance of multiple kallikreins in high-grade astrocytoma

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Drucker, Kristen L.; Gianinni, Caterina; Decker, Paul A.; Diamandis, Eleftherios P.; Scarisbrick, Isobel A.

2015-01-01

Kallikreins have clinical value as prognostic markers in a subset of malignancies examined to date, including kallikrein 3 (prostate specific antigen) in prostate cancer. We previously demonstrated that kallikrein 6 is expressed at higher levels in grade IV compared to grade III astrocytoma and is associated with reduced survival of GBM patients. In this study we determined KLK1, KLK6, KLK7, KLK8, KLK9 and KLK10 protein expression in two independent tissue microarrays containing 60 grade IV and 8 grade III astrocytoma samples. Scores for staining intensity, percent of tumor stained and immunoreactivity scores (IR, product of intensity and percent) were determined and analyzed for correlation with patient survival. Grade IV glioma was associated with higher levels of kallikrein-immunostaining compared to grade III specimens. Univariable Cox proportional hazards regression analysis demonstrated that elevated KLK6- or KLK7-IR was associated with poor patient prognosis. In addition, an increased percent of tumor immunoreactive for KLK6 or KLK9 was associated with decreased survival in grade IV patients. Kaplan-Meier survival analysis indicated that patients with KLK6-IR < 10, KLK6 percent tumor core stained < 3, or KLK7-IR < 9 had a significantly improved survival. Multivariable analysis indicated that the significance of these parameters was maintained even after adjusting for gender and performance score. These data suggest that elevations in glioblastoma KLK6, KLK7 and KLK9 protein have utility as prognostic markers of patient survival. The online version of this article (doi:10.1186/s12885-015-1566-5) contains supplementary material, which is available to authorized users

Kinin B1 receptors contributes to acute pain following minor surgery in humans

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Brahim Jaime S

2010-02-01

Full Text Available Abstract Background Kinins play an important role in regulation of pain and hyperalgesia after tissue injury and inflammation by activating two types of G-protein-coupled receptors, the kinin B1 and B2 receptors. It is generally accepted that the B2 receptor is constitutively expressed, whereas the B1 receptor is induced in response to inflammation. However, little is known about the regulatory effects of kinin receptors on the onset of acute inflammation and inflammatory pain in humans. The present study investigated the changes in gene expression of kinin receptors and the levels of their endogenous ligands at an early time point following tissue injury and their relation to clinical pain, as well as the effect of COX-inhibition on their expression levels. Results Tissue injury resulted in a significant up-regulation in the gene expression of B1 and B2 receptors at 3 hours post-surgery, the onset of acute inflammatory pain. Interestingly, the up-regulation in the gene expression of B1 and B2 receptors was positively correlated to pain intensity only after ketorolac treatment, signifying an interaction between prostaglandins and kinins in the inflammatory pain process. Further, the gene expression of both B1 and B2 receptors were correlated. Following tissue injury, B1 ligands des-Arg9-BK and des-Arg10-KD were significantly lower at the third hour compared to the first 2 hours in both the placebo and the ketorolac treatment groups but did not differ significantly between groups. Tissue injury also resulted in the down-regulation of TRPV1 gene expression at 3 hours post-surgery with no significant effect by ketorolac treatment. Interestingly, the change in gene expression of TRPV1 was correlated to the change in gene expression of B1 receptor but not B2 receptor. Conclusions These results provide evidence at the transcriptional level in a clinical model of tissue injury that up-regulation of kinin receptors are involved in the development of the

Radioimmunoassay of glandular kallikrein in human plasma after partial purification by immunoaffinity column

International Nuclear Information System (INIS)

Nishimura, Kazutaka; Inoue, Yoshikazu; Kokubu, Tatsuo

1987-01-01

Glandular kallikrein in human plasma was partially purified by immunoaffinity column and was measured by a radioimmunoassay (RIA). Plasma was diluted with an equal volume of 10 mmol/l sodium phosphate buffer, pH 7.4, containing 0.9% NaCl (PBS) and was applied to an immunoaffinity column from which glandular kallikrein was eluted with 3 mol/l NaSCN (20 ml). The enzymic fraction was concentrated with an Amicon PM 10 filter and dialyzed against PBS. The final recovery of the enzyme was 51.6 ± 1.6%, determined by using [ 125 I]kallikrein. The usable range of the standard curve covered 2.5-100 ng/tube. The coefficient of variation within the series was 5.9%, and the coefficient of variation between the series was 7.6%. In healthy controls, the plasma content of glandular kallikrein was 1.36 ± 0.39 ng/ml. In patients with acute pancreatitis, the plasma concentration was 8.02 ± 6.15 ng/ml, significantly different from the control group. (Auth.)

Discovery of novel transcripts of the human tissue kallikrein (KLK1) and kallikrein-related peptidase 2 (KLK2) in human cancer cells, exploiting Next-Generation Sequencing technology.

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Adamopoulos, Panagiotis G; Kontos, Christos K; Scorilas, Andreas

2018-03-31

Tissue kallikrein, kallikrein-related peptidases (KLKs), and plasma kallikrein form the largest group of serine proteases in the human genome, sharing many structural and functional properties. Several KLK transcripts have been found aberrantly expressed in numerous human malignancies, confirming their prognostic or/and diagnostic values. However, the process of alternative splicing can now be studied in-depth due to the development of Next-Generation Sequencing (NGS). In the present study, we used NGS to discover novel transcripts of the KLK1 and KLK2 genes, after nested touchdown PCR. Bioinformatics analysis and PCR experiments revealed a total of eleven novel KLK transcripts (two KLK1 and nine KLK2 transcripts). In addition, the expression profiles of each novel transcript were investigated with nested PCR experiments using variant-specific primers. Since KLKs are implicated in human malignancies, qualifying as potential biomarkers, the quantification of the presented novel transcripts in human samples may have clinical applications in different types of cancer. Copyright © 2018. Published by Elsevier Inc.

A positive association between the human tissue kallikerin gene A2233C polymorphism and blood pressure response to benazepril.

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Hong, Zhe; Pan, Liying; Fei, Jiali; Ma, Zhangqing; Hong, Zongyuan

2017-01-01

It is generally believed that essential hypertension is influenced by both genetic and environmental factors, as well as their interactions. Tissue kallikrein encoded by the tissue kallikrein gene (KLK1) is a key serine proteinase of kallikrein-kinin system, which is capable of generating potent vasactive peptides, kinins, by selective cleavage of the kininogen substrate. It was reported that the A2233 → C polymorphism in KLK1 gene is associated with essential hypertension. The aim of this study was to examine whether the molecular variations of KLK1 play role in determining the therapeutic response to benazepril, an ACE inhibitor. A total of 331 hypertensive individuals were recruited and treated with benazepril for 15 days. A variant impact of KLK1 A2233C was revealed. Chi-square analysis showed that the hypertensive subjects with the mutation genotype (AC + CC) had a higher proportion in systolic blood pressure (SBP, 88.1% vs. 79.0%, χ 2 = 4.141, p = 0.042) and diastolic blood pressure (DBP, 91.1% vs. 79.2%, χ 2 = 9.336, p = 0.002), respectively, to benazepril medication in good responders than in poor responders. Logistic regression analysis indicated that the hypertensive subjects with AC + CC genotype were more sensitive to the benazepril therapy in SBP (OR=1.97, 95% CI: 1.02-3.80, p = 0.044) and DBP (OR = 1.91, 95% CI: 2.69-5.16, p = 0.003), as compared with those hypertensive subjects with AA genotype. Our findings suggest that the A2233C polymorphism of KLK1 may be a marker of evaluation of hypertensive subjects' responses to angiotensin I converting enzyme inhibitors benazepril.

Comparative proteomics of cerebrospinal fluid reveals a predictive model for differential diagnosis of pneumococcal, meningococcal, and enteroviral meningitis, and novel putative therapeutic targets

Science.gov (United States)

2015-01-01

Background Meningitis is the inflammation of the meninges in response to infection or chemical agents. While aseptic meningitis, most frequently caused by enteroviruses, is usually benign with a self-limiting course, bacterial meningitis remains associated with high morbidity and mortality rates, despite advances in antimicrobial therapy and intensive care. Fast and accurate differential diagnosis is crucial for assertive choice of the appropriate therapeutic approach for each form of meningitis. Methods We used 2D-PAGE and mass spectrometry to identify the cerebrospinal fluid proteome specifically related to the host response to pneumococcal, meningococcal, and enteroviral meningitis. The disease-specific proteome signatures were inspected by pathway analysis. Results Unique cerebrospinal fluid proteome signatures were found to the three aetiological forms of meningitis investigated, and a qualitative predictive model with four protein markers was developed for the differential diagnosis of these diseases. Nevertheless, pathway analysis of the disease-specific proteomes unveiled that Kallikrein-kinin system may play a crucial role in the pathophysiological mechanisms leading to brain damage in bacterial meningitis. Proteins taking part in this cellular process are proposed as putative targets to novel adjunctive therapies. Conclusions Comparative proteomics of cerebrospinal fluid disclosed candidate biomarkers, which were combined in a qualitative and sequential predictive model with potential to improve the differential diagnosis of pneumococcal, meningococcal and enteroviral meningitis. Moreover, we present the first evidence of the possible implication of Kallikrein-kinin system in the pathophysiology of bacterial meningitis. PMID:26040285

Plasma kallikrein enhances platelet aggregation response by subthreshold doses of ADP.

Science.gov (United States)

Ottaiano, Tatiana F; Andrade, Sheila S; de Oliveira, Cleide; Silva, Mariana C C; Buri, Marcus V; Juliano, Maria A; Girão, Manoel J B C; Sampaio, Misako U; Schmaier, Alvin H; Wlodawer, Alexander; Maffei, Francisco H A; Oliva, Maria Luiza V

2017-04-01

Human plasma kallikrein (huPK) potentiates platelet responses to subthreshold doses of ADP, although huPK itself, does not induce platelet aggregation. In the present investigation, we observe that huPK pretreatment of platelets potentiates ADP-induced platelet activation by prior proteolysis of the G-protein-coupled receptor PAR-1. The potentiation of ADP-induced platelet activation by huPK is mediated by the integrin α IIb β 3 through interactions with the KGD/KGE sequence motif in huPK. Integrin α IIb β 3 is a cofactor for huPK binding to platelets to support PAR-1 hydrolysis that contributes to activation of the ADP signaling pathway. This activation pathway leads to phosphorylation of Src, AktS 473 , ERK1/2, and p38 MAPK, and to Ca 2+ release. The effect of huPK is blocked by specific antagonists of PAR-1 (SCH 19197) and α IIb β 3 (abciximab) and by synthetic peptides comprising the KGD and KGE sequence motifs of huPK. Further, recombinant plasma kallikrein inhibitor, rBbKI, also blocks this entire mechanism. These results suggest a new function for huPK. Formation of plasma kallikrein lowers the threshold for ADP-induced platelet activation. The present observations are consistent with the notion that plasma kallikrein promotes vascular disease and thrombosis in the intravascular compartment and its inhibition may ameliorate cardiovascular disease and thrombosis. Copyright © 2017 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

Arginine-esterase activity of kallikrein in the sera of whole-body irradiated rats and guinea-pigs

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Pouckova, P; Pospisil, J; Dienstbier, Z [Karlova Univ., Prague (Czechoslovakia). Biofyzikalni Ustav

1977-09-01

In whole-body irradiated rats (800 R=LDsub(50/30)) and guinea pigs (300 R=LDsub(50/30)) changes were investigated in the arginine esterase activity of kallikrein in native serum as well as in serum exposed to contact with a clay suspension. From the values obtained the activity of prekallikrein was calculated. While in the rat serum significant changes in the arginine esterase activity of kallikrein were found, in the guinea pig serum the kallikrein activity did not change markedly. The activity of prekallikrein immediately after irradiation assumes a similar course in both types of laboratory animals while during later intervals a reverse pattern was observed.

Kinin B1 receptors mediate depression-like behavior response in stressed mice treated with systemic E. coli lipopolysaccharide

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Campos Maria M

2010-12-01

Full Text Available Abstract Background Kinin B1 receptors are inducible molecules up-regulated after inflammatory stimuli. This study evaluated the relevance of kinin B1 receptors in a mouse depression behavior model. Methods Mice were exposed to a 5-min swimming session, and 30 min later they were injected with E. coli lipopolysaccharide (LPS. Depression-like behavior was assessed by determining immobility time in a tail suspension test. Different brain structures were collected for molecular and immunohistochemical studies. Anhedonia was assessed by means of a sucrose intake test. Results Our protocol elicited an increase in depression-like behavior in CF1 mice, as assessed by the tail-suspension test, at 24 h. This behavior was significantly reduced by treatment with the selective B1 receptor antagonists R-715 and SSR240612. Administration of SSR240612 also prevented an increase in number of activated microglial cells in mouse hippocampus, but did not affect a reduction in expression of mRNA for brain-derived neurotrophic factor. The increased immobility time following LPS treatment was preceded by an enhancement of hippocampal and cortical B1 receptor mRNA expression (which were maximal at 1 h, and a marked production of TNFα in serum, brain and cerebrospinal fluid (between 1 and 6 h. The depression-like behavior was virtually abolished in TNFα p55 receptor-knockout mice, and increased B1 receptor mRNA expression was completely absent in this mouse strain. Furthermore, treatment with SSR240612 was also effective in preventing anhedonia in LPS-treated mice, as assessed using a sucrose preference test. Conclusion Our data show, for the first time, involvement of kinin B1 receptors in depressive behavioral responses, in a process likely associated with microglial activation and TNFα production. Thus, selective and orally active B1 receptor antagonists might well represent promising pharmacological tools for depression therapy.

Kinin B1 receptor blockade and ACE inhibition attenuate cardiac postinfarction remodeling and heart failure in rats

International Nuclear Information System (INIS)

Lin, Xinchun; Bernloehr, Christian; Hildebrandt, Tobias; Stadler, Florian J.; Doods, Henri; Wu, Dongmei

2016-01-01

Introduction: The aim of the present study was to evaluate the effects of the novel kinin B1 receptor antagonist BI113823 on postinfarction cardiac remodeling and heart failure, and to determine whether B1 receptor blockade alters the cardiovascular effects of an angiotensin 1 converting enzyme (ACE) inhibitor in rats. Methods and results: Sprague Dawley rats were subjected to permanent occlusion of the left coronary artery. Cardiovascular function was determined at 6 weeks postinfarction. Treatment with either B1 receptor antagonist (BI113823) or an ACE inhibitor (lisinopril) alone or in combination significantly reduced the heart weight-to-body weight and lung weight-to-body weight ratios, and improved postinfarction cardiac function as evidenced by greater cardiac output, the maximum rate of left ventricular pressure rise (± dP/dtmax), left ventricle ejection fraction, fractional shorting, better wall motion, and attenuation of elevated left ventricular end diastolic pressure (LVEDP). Furthermore, all three treatment groups exhibited significant reduction in cardiac interstitial fibrosis, collagen deposition, CD68 positive macrophages, neutrophils, and proinflammatory cytokine production (TNF-α and IL-1β), compared to vehicle controls. Conclusion: The present study shows that treatment with the novel kinin B1 receptor antagonist, BI113823, reduces postinfarction cardiac remodeling and heart failure, and does not influence the cardiovascular effects of the ACE inhibitor. - Highlights: • We examined the role of kinin B1 receptors in the development of heart failure. • Kinin B1 receptor blockade attenuates post-infarction cardiac remodeling. • Kinin B1 receptor blockade improves dysfunction, and prevented heart failure. • B1 receptor blockade does not affect the cardio-protection of an ACE inhibitor.

Kinin B1 receptor blockade and ACE inhibition attenuate cardiac postinfarction remodeling and heart failure in rats

Energy Technology Data Exchange (ETDEWEB)

Lin, Xinchun [Department of Research, Mount Sinai Medical Center, Miami Beach, FL 33140 (United States); Bernloehr, Christian; Hildebrandt, Tobias [Boehringer Ingelheim Pharma GmbH & Co.KG, Biberach (Germany); Stadler, Florian J., E-mail: fjstadler@szu.edu.cn [Shenzhen Engineering Laboratory for Advanced Technology of Ceramics, Shenzhen 518060 (China); Doods, Henri [Boehringer Ingelheim Pharma GmbH & Co.KG, Biberach (Germany); Wu, Dongmei, E-mail: dongmeiwu@bellsouth.net [Department of Research, Mount Sinai Medical Center, Miami Beach, FL 33140 (United States); Department of BIN Convergence Technology, Chonbuk National University (Korea, Republic of)

2016-08-15

Introduction: The aim of the present study was to evaluate the effects of the novel kinin B1 receptor antagonist BI113823 on postinfarction cardiac remodeling and heart failure, and to determine whether B1 receptor blockade alters the cardiovascular effects of an angiotensin 1 converting enzyme (ACE) inhibitor in rats. Methods and results: Sprague Dawley rats were subjected to permanent occlusion of the left coronary artery. Cardiovascular function was determined at 6 weeks postinfarction. Treatment with either B1 receptor antagonist (BI113823) or an ACE inhibitor (lisinopril) alone or in combination significantly reduced the heart weight-to-body weight and lung weight-to-body weight ratios, and improved postinfarction cardiac function as evidenced by greater cardiac output, the maximum rate of left ventricular pressure rise (± dP/dtmax), left ventricle ejection fraction, fractional shorting, better wall motion, and attenuation of elevated left ventricular end diastolic pressure (LVEDP). Furthermore, all three treatment groups exhibited significant reduction in cardiac interstitial fibrosis, collagen deposition, CD68 positive macrophages, neutrophils, and proinflammatory cytokine production (TNF-α and IL-1β), compared to vehicle controls. Conclusion: The present study shows that treatment with the novel kinin B1 receptor antagonist, BI113823, reduces postinfarction cardiac remodeling and heart failure, and does not influence the cardiovascular effects of the ACE inhibitor. - Highlights: • We examined the role of kinin B1 receptors in the development of heart failure. • Kinin B1 receptor blockade attenuates post-infarction cardiac remodeling. • Kinin B1 receptor blockade improves dysfunction, and prevented heart failure. • B1 receptor blockade does not affect the cardio-protection of an ACE inhibitor.

Eco-Friendly Insecticide Discovery via Peptidomimetics: Design, Synthesis, and Aphicidal Activity of Novel Insect Kinin Analogues.

Science.gov (United States)

Zhang, Chuanliang; Qu, Yanyan; Wu, Xiaoqing; Song, Dunlun; Ling, Yun; Yang, Xinling

2015-05-13

Insect kinin neuropeptides are pleiotropic peptides that are involved in the regulation of hindgut contraction, diuresis, and digestive enzyme release. They share a common C-terminal pentapeptide sequence of Phe(1)-Xaa(2)-Yaa(3)-Trp(4)-Gly(5)-NH2 (where Xaa(2) = His, Asn, Phe, Ser, or Tyr; Yaa(3) = Pro, Ser, or Ala). Recently, the aphicidal activity of insect kinin analogues has attracted the attention of researchers. Our previous work demonstrated that the sequence-simplified insect kinin pentapeptide analogue Phe-Phe-[Aib]-Trp-Gly-NH2 could retain good aphicidal activity and be the lead compound for the further discovery of eco-friendly insecticides which encompassed a broad array of biochemicals derived from micro-organisms and other natural sources. Using the peptidomimetics strategy, we chose Phe-Phe-[Aib]-Trp-Gly-NH2 as the lead compound, and we designed and synthesized three series, including 31 novel insect kinin analogues. The aphicidal activity of the new analogues against soybean aphid was determined. The results showed that all of the analogues exhibited aphicidal activity. Of particular interest was the analogue II-1, which exhibited improved aphicidal activity with an LC50 of 0.019 mmol/L compared with the lead compound (LC50 = 0.045 mmol/L) or the commercial insecticide pymetrozine (LC50 = 0.034 mmol/L). This suggests that the analogue II-1 could be used as a new lead for the discovery of potential eco-friendly insecticides.

Nuclei of dwarf spheroidal galaxies KKs3 and ESO269-66 and their counterparts in our Galaxy

OpenAIRE

Sharina, M. E.; Shimansky, V. V.; Kniazev, A. Y.

2017-01-01

We present the analysis of medium-resolution spectra obtained at the Southern African Large Telescope (SALT) for nuclear globular clusters (GCs) in two dwarf spheroidal galaxies (dSphs). The galaxies have similar star formation histories, but they are situated in completely different environments. ESO269-66 is a close neighbour of the giant S0 NGC5128. KKs3 is one of the few truly isolated dSphs within 10 Mpc. We estimate the helium abundance $Y=0.3$, $\\rm age=12.6\\pm1$ Gyr, $[Fe/H]=-1.5,-1.5...

Component codification and identification systems

International Nuclear Information System (INIS)

Pannenbaecker, K.

1977-01-01

The lecture covers the codification in power stations during the erection phase and commercial operation phase. A diagram gives a survey. There are three basic-codifications for application; 1) Kraftwerk-Kennzeichen-System (KKS) for marking each component in orientated systems, for marking electrical orientated positions in cubicals, switch gears etc. and for marking rooms in buildings; 2) Ordnungssystem (OS) for cost calculation and ordering; 3) Unterlagenarten-Schluessel (UAS) for letters, reports etc. and for documentation. The OS is developed on the principle of cost account number and is therefore close to the organization of each supplier and his special form of design and constrution. KKS has only to mark hardware. Therefore all German owners, consultants, authorities and suppliers develop KKS together and conform to it in DIN 407119. (ORU) [de

Differential regulation of collagen secretion by kinin receptors in cardiac fibroblast and myofibroblast

Energy Technology Data Exchange (ETDEWEB)

Catalán, Mabel; Smolic, Christian [Centro de estudios moleculares de la célula, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile (Chile); Contreras, Ariel [Instituto Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile (Chile); Ayala, Pedro; Olmedo, Ivonne; Copaja, Miguel; Boza, Pía; Vivar, Raúl; Avalos, Yennifer [Centro de estudios moleculares de la célula, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile (Chile); Lavandero, Sergio [Centro de estudios moleculares de la célula, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile (Chile); Instituto Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile (Chile); Department of Internal Medicine (Cardiology Division), University of Texas Southwestern Medical Center, Dallas, TX (United States); Velarde, Victoria [Departamento de Ciencias Fisiológicas, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago (Chile); Díaz-Araya, Guillermo, E-mail: gadiaz@ciq.uchile.cl [Centro de estudios moleculares de la célula, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile (Chile)

2012-06-15

Kinins mediate their cellular effects through B1 (B1R) and B2 (B2R) receptors, and the activation of B2R reduces collagen synthesis in cardiac fibroblasts (CF). However, the question of whether B1R and/or B2R have a role in cardiac myofibroblasts remains unanswered. Methods: CF were isolated from neonate rats and myofibroblasts were generated by an 84 h treatment with TGF-β1 (CMF). B1R was evaluated by western blot, immunocytochemistry and radioligand assay; B2R, inducible nitric oxide synthase (iNOS), endothelial nitric oxide synthase (eNOS), and cyclooxygenases 1and 2 (COX-1, and COX-2) were evaluated by western blot; intracellular Ca{sup +2} levels were evaluated with Fluo-4AM; collagen secretion was measured in the culture media using the picrosirius red assay kit. Results: B2R, iNOS, COX-1 and low levels of B1R but not eNOS, were detected by western blot in CF. Also, B1R, B2R, and COX-2 but not iNOS, eNOS or COX-1, were detected by western blot in CMF. By immunocytochemistry, our results showed lower intracellular B1R levels in CF and higher B1R levels in CMF, mainly localized on the cell membrane. Additionally, we found B1R only in CMF cellular membrane through radioligand displacement assay. Bradykinin (BK) B2R agonist increased intracellular Ca{sup 2+} levels and reduced collagen secretion both in CF and CMF. These effects were blocked by HOE-140, and inhibited by L-NAME, 1400W and indomethacin. Des-Arg-kallidin (DAKD) B1R agonist did not increase intracellular Ca{sup 2+} levels in CF; however, after preincubation for 1 h with DAKD and re-stimulation with the same agonist, we found a low increase in intracellular Ca{sup 2+} levels. Finally, DAKD increased intracellular Ca{sup 2+} levels and decreased collagen secretion in CMF, being this effect blocked by the B1R antagonist des-Arg9-Leu8-kallidin and indomethacin, but not by L-NAME or 1400 W. Conclusion: B1R, B2R, iNOS and COX-1 were expressed differently between CF and CMF, and collagen secretion was

Differential regulation of collagen secretion by kinin receptors in cardiac fibroblast and myofibroblast

International Nuclear Information System (INIS)

Catalán, Mabel; Smolic, Christian; Contreras, Ariel; Ayala, Pedro; Olmedo, Ivonne; Copaja, Miguel; Boza, Pía; Vivar, Raúl; Avalos, Yennifer; Lavandero, Sergio; Velarde, Victoria; Díaz-Araya, Guillermo

2012-01-01

Kinins mediate their cellular effects through B1 (B1R) and B2 (B2R) receptors, and the activation of B2R reduces collagen synthesis in cardiac fibroblasts (CF). However, the question of whether B1R and/or B2R have a role in cardiac myofibroblasts remains unanswered. Methods: CF were isolated from neonate rats and myofibroblasts were generated by an 84 h treatment with TGF-β1 (CMF). B1R was evaluated by western blot, immunocytochemistry and radioligand assay; B2R, inducible nitric oxide synthase (iNOS), endothelial nitric oxide synthase (eNOS), and cyclooxygenases 1and 2 (COX-1, and COX-2) were evaluated by western blot; intracellular Ca +2 levels were evaluated with Fluo-4AM; collagen secretion was measured in the culture media using the picrosirius red assay kit. Results: B2R, iNOS, COX-1 and low levels of B1R but not eNOS, were detected by western blot in CF. Also, B1R, B2R, and COX-2 but not iNOS, eNOS or COX-1, were detected by western blot in CMF. By immunocytochemistry, our results showed lower intracellular B1R levels in CF and higher B1R levels in CMF, mainly localized on the cell membrane. Additionally, we found B1R only in CMF cellular membrane through radioligand displacement assay. Bradykinin (BK) B2R agonist increased intracellular Ca 2+ levels and reduced collagen secretion both in CF and CMF. These effects were blocked by HOE-140, and inhibited by L-NAME, 1400W and indomethacin. Des-Arg-kallidin (DAKD) B1R agonist did not increase intracellular Ca 2+ levels in CF; however, after preincubation for 1 h with DAKD and re-stimulation with the same agonist, we found a low increase in intracellular Ca 2+ levels. Finally, DAKD increased intracellular Ca 2+ levels and decreased collagen secretion in CMF, being this effect blocked by the B1R antagonist des-Arg9-Leu8-kallidin and indomethacin, but not by L-NAME or 1400 W. Conclusion: B1R, B2R, iNOS and COX-1 were expressed differently between CF and CMF, and collagen secretion was regulated differentially by

Kinins in ant venoms--a comparison with venoms of related Hymenoptera

NARCIS (Netherlands)

Piek, T.; Schmidt, J. O.; de Jong, J. M.; Mantel, P.

1989-01-01

1. Venom preparations have been made of six ant, one pompilid wasp, two mutillid wasp, and four social wasp species. 2. The venoms were analysed pharmacologically in order to detect kinin-like activity. 3. Due to the small amounts of venoms available only a cascade of smooth muscle preparation could

Functional and molecular characterization of kinin B1 and B 2 receptors in human bladder cancer: implication of the PI3Kγ pathway.

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Sgnaolin, V; Pereira, T C B; Bogo, M R; Zanin, R; Battastini, A M O; Morrone, F B; Campos, M M

2013-08-01

Kinins and their receptors have been recently implicated in cancer. Using functional and molecular approaches, we investigated the relevance of kinin B1 and B2 receptors in bladder cancer. Functional studies were conducted using bladder cancer cell lines, and human biopsies were employed for molecular studies. Both B1 des-Arg(9)-BK and B2 BK receptor agonists stimulated the proliferation of grade 3-derived T24 bladder cancer cells. Furthermore, treatment with B1 and B2 receptor antagonists (SSR240612 and HOE140) markedly inhibited the proliferation of T24 cells. Only higher concentrations of BK increased the proliferation of the grade 1 bladder cancer cell line RT4, while des-Arg(9)-BK completely failed to induce its proliferation. Real-time PCR revealed that the mRNA expression of kinin receptors, particularly B1 receptors, was increased in T24 cells relative to RT4 cells. Data from bladder cancer human biopsies revealed that B1 receptor expression was increased in all tumor samples and under conditions of chronic inflammation. We also show novel evidence demonstrating that the pharmacological inhibition of PI3Kγ (phosphatidylinositol 3-kinase) with AS252424, concentration-dependently reduced T24 cell proliferation induced by BK or des-Arg(9)-BK. Finally, the incubation of T24 cells with kinin agonists led to a marked activation of the PI3K/AKT and ERK 1/2 signaling pathways, whereas p38 MAP kinase remained unaffected. Kinin receptors, especially B1 receptors, appear to be implicated in bladder cancer progression. It is tempting to suggest that selective kinin antagonists might represent potential alternative therapies for bladder cancer.

Key role for spinal dorsal horn microglial kinin B1 receptor in early diabetic pain neuropathy

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Couture Réjean

2010-06-01

Full Text Available Abstract Background The pro-nociceptive kinin B1 receptor (B1R is upregulated on sensory C-fibres, astrocytes and microglia in the spinal cord of streptozotocin (STZ-diabetic rat. This study aims at defining the role of microglial kinin B1R in diabetic pain neuropathy. Methods Sprague-Dawley rats were made diabetic with STZ (65 mg/kg, i.p., and 4 days later, two specific inhibitors of microglial cells (fluorocitrate, 1 nmol, i.t.; minocycline, 10 mg/kg, i.p. were administered to assess the impact on thermal hyperalgesia, allodynia and mRNA expression (qRT-PCR of B1R and pro-inflammatory markers. Spinal B1R binding sites ((125I-HPP-desArg10-Hoe 140 were also measured by quantitative autoradiography. Inhibition of microglia was confirmed by confocal microscopy with the specific marker Iba-1. Effects of intrathecal and/or systemic administration of B1R agonist (des-Arg9-BK and antagonists (SSR240612 and R-715 were measured on neuropathic pain manifestations. Results STZ-diabetic rats displayed significant tactile and cold allodynia compared with control rats. Intrathecal or peripheral blockade of B1R or inhibition of microglia reversed time-dependently tactile and cold allodynia in diabetic rats without affecting basal values in control rats. Microglia inhibition also abolished thermal hyperalgesia and the enhanced allodynia induced by intrathecal des-Arg9-BK without affecting hyperglycemia in STZ rats. The enhanced mRNA expression (B1R, IL-1β, TNF-α, TRPV1 and Iba-1 immunoreactivity in the STZ spinal cord were normalized by fluorocitrate or minocycline, yet B1R binding sites were reduced by 38%. Conclusion The upregulation of kinin B1R in spinal dorsal horn microglia by pro-inflammatory cytokines is proposed as a crucial mechanism in early pain neuropathy in STZ-diabetic rats.

A cytocidal tissue kallikrein isolated from mouse submandibular glands.

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Murakami, K; Ikigai, H; Nagumo, N; Tomita, M; Shimamura, T

1989-11-06

A cytocidal factor against mouse thymocytes was purified from the submandibular glands of female BALB/c mice using Sephadex G-50 gel filtration chromatography and reverse-phase HPLC. SDS-PAGE and amino acid sequence analysis revealed that the cytocidal factor was mouse glandular kallikrein (mGK)-6. mGK-6 showed an optimal enzyme activity at pH 10 and a cytocidal activity against thymocytes in a dose-dependent manner.

Twenty-year Risk of Prostate Cancer Death by Midlife Prostate-specific Antigen and a Panel of Four Kallikrein Markers in a Large Population-based Cohort of Healthy Men.

Science.gov (United States)

Sjoberg, Daniel D; Vickers, Andrew J; Assel, Melissa; Dahlin, Anders; Poon, Bing Ying; Ulmert, David; Lilja, Hans

2018-06-01

Prostate-specific antigen (PSA) screening reduces prostate cancer deaths but leads to harm from overdiagnosis and overtreatment. To determine the long-term risk of prostate cancer mortality using kallikrein blood markers measured at baseline in a large population of healthy men to identify men with low risk for prostate cancer death. Study based on the Malmö Diet and Cancer cohort enrolling 11 506 unscreened men aged 45-73 yr during 1991-1996, providing cryopreserved blood at enrollment and followed without PSA screening to December 31, 2014. We measured four kallikrein markers in the blood of 1223 prostate cancer cases and 3028 controls. Prostate cancer death (n=317) by PSA and a prespecified statistical model based on the levels of four kallikrein markers. Baseline PSA predicted prostate cancer death with a concordance index of 0.86. In men with elevated PSA (≥2.0ng/ml), predictive accuracy was enhanced by the four-kallikrein panel compared with PSA (0.80 vs 0.73; improvement 0.07; 95% confidence interval 0.04, 0.10). Nearly half of men aged 60+ yr with elevated PSA had a four-kallikrein panel score of four-kallikrein panel score of ≥7.5% had a 13% risk of prostate cancer death at 15 yr. A prespecified statistical model based on four kallikrein markers (commercially available as the 4Kscore) reclassified many men with modestly elevated PSA, to have a low long-term risk of prostate cancer death. Men with elevated PSA but low scores from the four-kallikrein panel can be monitored rather than being subject to biopsy. Men with elevated prostate-specific antigen (PSA) are often referred for prostate biopsy. However, men with elevated PSA but low scores from the four-kallikrein panel can be monitored rather than being subject to biopsy. Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.

The Kallikrein Inhibitor from Bauhinia bauhinioides (BbKI) shows antithrombotic properties in venous and arterial thrombosis models.

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Brito, Marlon V; de Oliveira, Cleide; Salu, Bruno R; Andrade, Sonia A; Malloy, Paula M D; Sato, Ana C; Vicente, Cristina P; Sampaio, Misako U; Maffei, Francisco H A; Oliva, Maria Luiza V

2014-05-01

The Bauhinia bauhinioides Kallikrein Inhibitor (BbKI) is a Kunitz-type serine peptidase inhibitor of plant origin that has been shown to impair the viability of some tumor cells and to feature a potent inhibitory activity against human and rat plasma kallikrein (Kiapp 2.4 nmol/L and 5.2 nmol/L, respectively). This inhibitory activity is possibly responsible for an effect on hemostasis by prolonging activated partial thromboplastin time (aPTT). Because the association between cancer and thrombosis is well established, we evaluated the possible antithrombotic activity of this protein in venous and arterial thrombosis models. Vein thrombosis was studied in the vena cava ligature model in Wistar rats, and arterial thrombosis in the photochemical induced endothelium lesion model in the carotid artery of C57 black 6 mice. BbKI at a concentration of 2.0 mg/kg reduced the venous thrombus weight by 65% in treated rats in comparison to rats in the control group. The inhibitor prolonged the time for total artery occlusion in the carotid artery model mice indicating that this potent plasma kallikrein inhibitor prevented thrombosis. Copyright © 2014 Elsevier Ltd. All rights reserved.

Critical role of tissue kallikrein in vessel formation and maturation : Implications for therapeutic revascularization

NARCIS (Netherlands)

Stone, O.A.; Richer, C.; Emanueli, C.; Weel, V. van; Quax, P.H.A.; Katare, R.; Kraenkel, N.; Campagnolo, P.; Barcelos, L.S.; Siragusa, M.; Sala-Newby, G.B.; Baldessari, D.; Mione, M.; Vincent, M.P.; Benest, A.V.; Al Haj Zen, A.; Gonzalez, J.; Bates, D.O.; Alhenc-Gelas, F.; Madeddu, P.

2009-01-01

OBJECTIVE : Human Tissue Kallikrein (hKLK1) overexpression promotes an enduring neovascularization of ischemic tissue, yet the cellular mechanisms of hKLK1-induced arteriogenesis remain unknown. Furthermore, no previous study has compared the angiogenic potency of hKLK1, with its loss of function

Plasminogen-independent initiation of the pro-urokinase activation cascade in vivo. Activation of pro-urokinase by glandular kallikrein (mGK-6) in plasminogen-deficient mice

DEFF Research Database (Denmark)

List, K; Jensen, Ole Nørregaard; Bugge, T H

2000-01-01

)-antitrypsin. We suggest that mouse glandular kallikrein mGK-6 is an activator of pro-uPA in the mouse urinary tract in vivo. Since this kallikrein is expressed in a number of tissues and also occurs in plasma, it can also be considered a candidate for a physiological pro-uPA activator in other locations....

Plasma extravasation mediated by lipopolysaccharide-induction of kinin B1 receptors in rat tissues

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Paulo Roberto Wille

2001-01-01

Full Text Available The present study was performed to: (a evaluate the effects of kinin B1 (Sar{D-Phe8}-des-Arg9-BK; 10 nmol/kg and B2 (bradykinin (BK; 10 nmol/kg receptor agonists on plasma extravasation in selected rat tissues; (b determine the contribution of a lipopolysaccharide (LPS (100 μ g/kg to the effects triggered by B1 and B2 agonists; and (c characterize the selectivity of B1 ({Leu8}desArg9-BK; 10 nmol/kg and B2 (HOE 140; 10 nmol/kg antagonists as inhibitors of this kinin-induced phenomenon. B1 and B2 agonists were shown to increase plasma extravasation in the duodenum, ileum and also in the urinary bladder of the rat. LPS pretreatment enhanced the plasma extravasation mediated only by the B1 agonist in the duodenum, ileum, trachea, main and segmentar bronchi. These effects were prevented by the B1. but not the B2 antagonist. In normal rats, the B2 antagonist inhibited the effect of B2 agonist in all the tissues analyzed. However, in LPS-treated rats, the B2 antagonist was ineffective in the urinary bladder.

Effect of pancreatic kallikrein combined with magnesium sulfate therapy on disease severity of patients with severe preeclampsia

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Yi Yang

2016-10-01

Full Text Available Objective: To study the clinical effect of pancreatic kallikrein combined with magnesium sulfate therapy on severe preeclampsia. Methods: A total of 47 patients with severe preeclampsia treated in our hospital from May 2013 to October 2015 were retrospectively analyzed, patients who received pancreatic kallikrein combined with magnesium sulfate therapy were selected as observation group, patients who received magnesium sulfate therapy were selected as control group, and then blood pressure level, renal function, uterine artery and umbilical artery blood flow state, and hypoxia indexes in serum and placenta were compared between two groups. Results: After treatment, systolic pressure and diastolic pressure levels as well as serum CysC level and 24 h urine protein level of observation group were significantly lower than those of control group, the uterine artery and umbilical artery S/ D and PI were significantly lower than those of control group, PIGF and NO levels in serum as well as Xiap and Survivin levels in placenta were significantly higher than those of control group, and sVEGFR1 level in serum as well as Caspase-3 and Caspase-7 levels in placenta was significantly lower than those of control group. Conclusions: Pancreatic kallikrein combined with magnesium sulfate therapy can alleviate the disease severity, lower blood pressure and vascular resistance, and improve renal function and the apoptosis caused by placental hypoxia in patients with severe preeclampsia.

Improving virtual screening predictive accuracy of Human kallikrein 5 inhibitors using machine learning models.

Science.gov (United States)

Fang, Xingang; Bagui, Sikha; Bagui, Subhash

2017-08-01

The readily available high throughput screening (HTS) data from the PubChem database provides an opportunity for mining of small molecules in a variety of biological systems using machine learning techniques. From the thousands of available molecular descriptors developed to encode useful chemical information representing the characteristics of molecules, descriptor selection is an essential step in building an optimal quantitative structural-activity relationship (QSAR) model. For the development of a systematic descriptor selection strategy, we need the understanding of the relationship between: (i) the descriptor selection; (ii) the choice of the machine learning model; and (iii) the characteristics of the target bio-molecule. In this work, we employed the Signature descriptor to generate a dataset on the Human kallikrein 5 (hK 5) inhibition confirmatory assay data and compared multiple classification models including logistic regression, support vector machine, random forest and k-nearest neighbor. Under optimal conditions, the logistic regression model provided extremely high overall accuracy (98%) and precision (90%), with good sensitivity (65%) in the cross validation test. In testing the primary HTS screening data with more than 200K molecular structures, the logistic regression model exhibited the capability of eliminating more than 99.9% of the inactive structures. As part of our exploration of the descriptor-model-target relationship, the excellent predictive performance of the combination of the Signature descriptor and the logistic regression model on the assay data of the Human kallikrein 5 (hK 5) target suggested a feasible descriptor/model selection strategy on similar targets. Copyright © 2017 Elsevier Ltd. All rights reserved.

The corticotropin-releasing factor-like diuretic hormone 44 (DH44) and kinin neuropeptides modulate desiccation and starvation tolerance in Drosophila melanogaster.

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Cannell, Elizabeth; Dornan, Anthony J; Halberg, Kenneth A; Terhzaz, Selim; Dow, Julian A T; Davies, Shireen-A

2016-06-01

Malpighian tubules are critical organs for epithelial fluid transport and stress tolerance in insects, and are under neuroendocrine control by multiple neuropeptides secreted by identified neurons. Here, we demonstrate roles for CRF-like diuretic hormone 44 (DH44) and Drosophila melanogaster kinin (Drome-kinin, DK) in desiccation and starvation tolerance. Gene expression and labelled DH44 ligand binding data, as well as highly selective knockdowns and/or neuronal ablations of DH44 in neurons of the pars intercerebralis and DH44 receptor (DH44-R2) in Malpighian tubule principal cells, indicate that suppression of DH44 signalling improves desiccation tolerance of the intact fly. Drome-kinin receptor, encoded by the leucokinin receptor gene, LKR, is expressed in DH44 neurons as well as in stellate cells of the Malpighian tubules. LKR knockdown in DH44-expressing neurons reduces Malpighian tubule-specific LKR, suggesting interactions between DH44 and LK signalling pathways. Finally, although a role for DK in desiccation tolerance was not defined, we demonstrate a novel role for Malpighian tubule cell-specific LKR in starvation tolerance. Starvation increases gene expression of epithelial LKR. Also, Malpighian tubule stellate cell-specific knockdown of LKR significantly reduced starvation tolerance, demonstrating a role for neuropeptide signalling during starvation stress. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Kallistatin Ameliorates Influenza Virus Pathogenesis by Inhibition of Kallikrein-Related Peptidase 1-Mediated Cleavage of Viral Hemagglutinin

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Leu, Chia-Hsing; Yang, Mei-Lin; Chung, Nai-Hui; Huang, Yen-Jang; Su, Yu-Chu; Chen, Yi-Cheng; Lin, Chia-Cheng; Shieh, Gia-Shing; Chang, Meng-Ya; Wang, Shainn-Wei; Chang, Yao; Chao, Julie; Chao, Lee

2015-01-01

Proteolytic cleavage of the hemagglutinin (HA) of influenza virus by host trypsin-like proteases is required for viral infectivity. Some serine proteases are capable of cleaving influenza virus HA, whereas some serine protease inhibitors (serpins) inhibit the HA cleavage in various cell types. Kallikrein-related peptidase 1 (KLK1, also known as tissue kallikrein) is a widely distributed serine protease. Kallistatin, a serpin synthesized mainly in the liver and rapidly secreted into the circulation, forms complexes with KLK1 and inhibits its activity. Here, we investigated the roles of KLK1 and kallistatin in influenza virus infection. We show that the levels of KLK1 increased, whereas those of kallistatin decreased, in the lungs of mice during influenza virus infection. KLK1 cleaved H1, H2, and H3 HA molecules and consequently enhanced viral production. In contrast, kallistatin inhibited KLK1-mediated HA cleavage and reduced viral production. Cells transduced with the kallistatin gene secreted kallistatin extracellularly, which rendered them more resistant to influenza virus infection. Furthermore, lentivirus-mediated kallistatin gene delivery protected mice against lethal influenza virus challenge by reducing the viral load, inflammation, and injury in the lung. Taking the data together, we determined that KLK1 and kallistatin contribute to the pathogenesis of influenza virus by affecting the cleavage of the HA peptide and inflammatory responses. This study provides a proof of principle for the potential therapeutic application of kallistatin or other KLK1 inhibitors for influenza. Since proteolytic activation also enhances the infectivity of some other viruses, kallistatin and other kallikrein inhibitors may be explored as antiviral agents against these viruses. PMID:26149981

The corticotropin-releasing factor-like diuretic hormone 44 (DH44) and kinin neuropeptides modulate desiccation and starvation tolerance in Drosophila melanogaster

DEFF Research Database (Denmark)

Cannell, Elizabeth; Dornan, Anthony J.; Halberg, Kenneth Agerlin

2016-01-01

Malpighian tubules are critical organs for epithelial fluid transport and stress tolerance in insects, and are under neuroendocrine control by multiple neuropeptides secreted by identified neurons. Here, we demonstrate roles for CRF-like diuretic hormone 44 (DH44) and Drosophila melanogaster kinin...

Renin inhibitor aliskiren exerts beneficial effect on trabecular bone by regulating skeletal renin-angiotensin system and kallikrein-kinin system in ovariectomized mice.

Science.gov (United States)

Zhang, Y; Wang, L; Song, Y; Zhao, X; Wong, M S; Zhang, W

2016-03-01

The skeletal renin-angiotensin system contributes to the development of osteoporosis. The renin inhibitor aliskiren exhibited beneficial effects on trabecular bone of osteoporotic mice, and this action might be mediated through angiotensin and bradykinin receptor pathways. This study implies the potential application of renin inhibitor in the management for postmenopausal osteoporosis. The skeletal renin-angiotensin system plays key role in the pathological process of osteoporosis. The present study is designed to elucidate the effect of renin inhibitor aliskiren on trabecular bone and its potential action mechanism in ovariectomized (OVX) mice. The OVX mice were treated with low dose (5 mg/kg) or high dose (25 mg/kg) of aliskiren or its vehicle for 8 weeks. The bone turnover markers were measured by ELISA. The structural parameters of trabecular bone at lumbar vertebra (LV) and distal femoral metaphysis were measured by micro-CT. The expression of messenger RNA (mRNA) and protein was studied by RT-PCR and immunoblotting, respectively. Aliskiren treatment reduced urinary excretion of calcium and serum level of tartrate-resistant acid phosphatase in OVX mice. The treatment with aliskiren significantly increased bone volume (BV/TV) and connectivity density (Conn.D) of trabecular bone at LV-2 and LV-5 as well as dramatically enhanced BV/TV, Conn.D, bone mineral density (BMD/BV) and decreased bone surface (BS/BV) at the distal femoral end. Aliskiren significantly down-regulated the expression of angiotensinogen, angiotensin II (Ang II), Ang II type 1 receptor, bradykinin receptor (BR)-1, and osteocytic-specific gene sclerostin as well as the osteoclast-specific genes, including carbonic anhydrase II, matrix metalloproteinase-9, and cathepsin K. This study revealed that renin inhibitor aliskiren exhibited the beneficial effects on trabecular bone of ovariectomy-induced osteoporotic mice, and the underlying mechanism for this action might be mediated through Ang II and

Role of endothelial dysfunction in the pathogenesis of diabetic retinopathy in patients with type 2 diabetes

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I. V. Vorobyeva

2014-07-01

Full Text Available The reason for the progressive vision reduction at diabetes mellitus (DM is diabetic retinopathy (DR. When type 2 diabetes combined with hypertension (Ht, it increases the risk of vision loss by 25 times. In the pathogenesis of DR is important to endothelial dysfunction and a variety of biochemical processes (an excess of intracellular sorbitol, non-enzymatic glycation of proteins, oxidative stress. there is a decrease in generation vasodilating factors, nitric oxide, with a simultaneous increase of endothelin, which causes vasoconstriction. Key processes underlying the development of DR, such as increased vascular permeability, edema, neovasculariza- tion, inflammation and associated with the effects of kallikrein-kinin system. In the pathogenesis of DR can be involved independent intraocular renin-angiotensin system, which is an important mediator of angiogenesis and increased vascular permeability. Damage to the endothelium of retinal vessels leads to ischemia of the retina. there is growth and development of newly formed blood vessels, which may provoke recurrent bleeding.

Autoradiographic research on cell proliferation of prenatal rat lung cells and their influence using the mitogen Kallikrein

International Nuclear Information System (INIS)

Bock-Lamberlin, P.R.

1980-01-01

In this work autoradiographic experiments were carried out on the kinetics of proliferation of four cell populations of the prenatal rat lung with the help of the determination of the 3 H-thymidine marker indices, with the following results: 1. The four studied cell populations exhibited variable proliferation rates on the twentieth or twenty-first day of development. 2. The strongest affect of the exogenously applied mitogen Kallikrein was demonstrated on the vessel wall cells, the next strongest on the bronchial epithelial cells, then the cartilage cells and finally the alveolar wall cells. 3. The mitogenic effect is dependent on dose. Higher doses significantly increased the 3 H-thymidine marker indices of the four cell populations tested in this work. 4. When the exposure time of the Kallikrein was extended by one hour this lead partially to stronger mitogenic effects than by the shorter exposure times at the same and higher dose levels of mitogen. 5. The 3 H-thymidine marker indices are dependent on the exposure time. 6. With increasing litter size, the 3 H indices as a rule decrease. (orig./MG) [de

Predictive value of four kallikrein markers for pathologically insignificant compared with aggressive prostate cancer in radical prostatectomy specimens: results from the European Randomized Study of Screening for Prostate Cancer section Rotterdam.

Science.gov (United States)

Carlsson, Sigrid; Maschino, Alexandra; Schröder, Fritz; Bangma, Chris; Steyerberg, Ewout W; van der Kwast, Theo; van Leenders, Geert; Vickers, Andrew; Lilja, Hans; Roobol, Monique J

2013-11-01

Treatment decisions can be difficult in men with low-risk prostate cancer (PCa). To evaluate the ability of a panel of four kallikrein markers in blood-total prostate-specific antigen (PSA), free PSA, intact PSA, and kallikrein-related peptidase 2-to distinguish between pathologically insignificant and aggressive disease on pathologic examination of radical prostatectomy (RP) specimens as well as to calculate the number of avoidable surgeries. The cohort comprised 392 screened men participating in rounds 1 and 2 of the Rotterdam arm of the European Randomized Study of Screening for Prostate Cancer. Patients were diagnosed with PCa because of an elevated PSA ≥3.0 ng/ml and were treated with RP between 1994 and 2004. We calculated the accuracy (area under the curve [AUC]) of statistical models to predict pathologically aggressive PCa (pT3-T4, extracapsular extension, tumor volume >0.5cm(3), or any Gleason grade ≥4) based on clinical predictors (age, stage, PSA, biopsy findings) with and without levels of four kallikrein markers in blood. A total of 261 patients (67%) had significant disease on pathologic evaluation of the RP specimen. While the clinical model had good accuracy in predicting aggressive disease, reflected in a corrected AUC of 0.81, the four kallikrein markers enhanced the base model, with an AUC of 0.84 (p limitation of the present study is that clinicians may be hesitant to make recommendations against active treatment on the basis of a statistical model. Our study provided proof of principle that predictions based on levels of four kallikrein markers in blood distinguish between pathologically insignificant and aggressive disease after RP with good accuracy. In the future, clinical use of the model could potentially reduce rates of immediate unnecessary active treatment. Copyright © 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Effect of bauhinia bauhinioides kallikrein inhibitor on endothelial proliferation and intracellular calcium concentration.

Science.gov (United States)

Bilgin, M; Burgazli, K M; Rafiq, A; Mericliler, M; Neuhof, C; Oliva, M L; Parahuleva, M; Soydan, N; Doerr, O; Abdallah, Y; Erdogan, A

2014-01-01

Proteinase inhibitors act as a defensive system against predators e.g. insects, in plants. Bauhinia bauhinioides kallikrein inhibitor (BbKI) is a serine proteinase inhibitor, isolated from seeds of Bauhinia bauhinioides and is structurally similar to plant Kunitz-type inhibitors but lacks disulfide bridges. In this study we evaluated the antiproliferative effect of BbKI on endothelial cells and its impact on changes in membrane potential and intracellular calcium. HUVEC proliferation was significantly reduced by incubation with BbKI 50 and 100 µM 12% and 13%. Furthermore, BbKI (100 µM) exposure caused a significant increase in intracellular Ca2+ concentration by 35% as compared to untreated control. The intracellular rise in calcium was not affected by the absence of extracellular calcium. BBKI also caused a significant change in the cell membrane potential but the antiproliferative effect was independent of changes in membrane potential. BBKI has an antiproliferative effect on HUVEC, which is independent of the changes in membrane potential, and it causes an increase in intracellular Ca2+.

Brain kinin B1 receptor is upregulated by the oxidative stress and its activation leads to stereotypic nociceptive behavior in insulin-resistant rats.

Science.gov (United States)

Dias, Jenny Pena; Gariépy, Helaine De Brito; Ongali, Brice; Couture, Réjean

2015-07-01

Kinin B1 receptor (B1R) is virtually absent under physiological condition, yet it is highly expressed in models of diabetes mellitus. This study aims at determining: (1) whether B1R is induced in the brain of insulin-resistant rat through the oxidative stress; (2) the consequence of B1R activation on stereotypic nocifensive behavior; (3) the role of downstream putative mediators in B1R-induced behavioral activity. Sprague-Dawley rats were fed with 10% D-glucose in their drinking water or tap water (controls) for 4 or 12 weeks, combined either with a standard chow diet or a diet enriched with α-lipoic acid (1 g/kg feed) for 4 weeks. The distribution and density of brain B1R binding sites were assessed by autoradiography. Behavioral activity evoked by i.c.v. injection of the B1R agonist Sar-[D-Phe(8)]-des-Arg(9)-BK (10 μg) was measured before and after i.c.v. treatments with selective antagonists (10 μg) for kinin B1 (R-715, SSR240612), tachykinin NK1 (RP-67580) and glutamate NMDA (DL-AP5) receptors or with the inhibitor of NOS (L-NNA). Results showed significant increases of B1R binding sites in various brain areas of glucose-fed rats that could be prevented by the diet containing α-lipoic acid. The B1R agonist elicited head scratching, grooming, sniffing, rearing, digging, licking, face washing, wet dog shake, teeth chattering and biting in glucose-fed rats, which were absent after treatment with α-lipoic acid or antagonists/inhibitors. Data suggest that kinin B1R is upregulated by the oxidative stress in the brain of insulin-resistant rats and its activation causes stereotypic nocifensive behavior through the release of substance P, glutamate and NO. Copyright © 2015 Elsevier Inc. All rights reserved.

Changes of the kallikrein-kinin system in the course of the postirradiation syndrome in rats and guinea pigs

International Nuclear Information System (INIS)

Pouckova, P.; Pospisil, J.; Dienstbier, Z.

1978-01-01

Within the study of the postirradiation distortion of the hemocoagulation and hemostasis changes were investigated of the level of prekallikrein, kininogens, and kininases in the blood serum and plasma of the whole-body irradiated animals. The rats and guinea pigs were exposed to 800 R (206.4 mC.kg -1 ) and 300 R (77.4 mC.kg -1 ), respectively, of 60 Co gamma rays which represented the LD 50/30 for the two species. In the observed postirradiation time intervals i.e. 10, 30, 60, 120 min, 6, 12 and 24 hrs the changes of the level of prekallikrein were idential with those of the level of prekallikrein in the blood serum whole-body irradiated guinea pigs. At 2, 4, 7, 10, 12 and 14 days after irradiation the course of the level of the prekallikrein in the blood serum of the rats and guinea pigs showed mutual mirror symmetry. Changes were observed of the level of kininogens in the blood plasma of the rats and guinea pigs after the exposures to 800 and 300 R, respectively. In this case, the level of kininogens in the rats and guinea pigs had changed similarly, in the guinea pigs, however, the changes of the level of kininogens varied within the range of control values. The level of kininases in the blood plasma of irradiated rats reached its maximum value on the 4th day after total irradiation, and later decreased. In the blood plasma of irradiated guinea pigs the course of the level of kininases was characterized by mirror symmetry, always with maximum and minimum values on the 7th day after total exposure. (author)

Activation of TAFI on the surface of Streptococcus pyogenes evokes inflammatory reactions by modulating the kallikrein/kinin system

NARCIS (Netherlands)

Bengtson, Sara H.; Sandén, Caroline; Mörgelin, Matthias; Marx, Pauline F.; Olin, Anders I.; Leeb-Lundberg, L. M. Fredrik; Meijers, Joost C. M.; Herwald, Heiko

2008-01-01

Bacteria-controlled regulation of host responses to infection is an important virulence mechanism that has been demonstrated to contribute to disease progression. Here we report that the human pathogen Streptococcus pyogenes employs the procarboxypeptidase TAFI (thrombin-activatable fibrinolysis

Role of kinin B1 and B2 receptors in memory consolidation during the aging process of mice.

Science.gov (United States)

Lemos, Mayra Tolentino Resk; Amaral, Fabio Agostini; Dong, Karis Ester; Bittencourt, Maria Fernanda Queiroz Prado; Caetano, Ariadiny Lima; Pesquero, João Bosco; Viel, Tania Araujo; Buck, Hudson Sousa

2010-04-01

Under physiological conditions, elderly people present memory deficit associated with neuronal loss. This pattern is also associated with Alzheimer's disease but, in this case, in a dramatically intensified level. Kinin receptors have been involved in neurodegeneration and increase of amyloid-beta concentration, associated with Alzheimer's disease (AD). Considering these findings, this work evaluated the role of kinin receptors in memory consolidation during the aging process. Male C57Bl/6 (wt), knock-out B1 (koB1) or B2 (koB2) mice (3, 6, 12 and 18-month-old - mo; n=10 per group) were submitted to an acquisition session, reinforcement to learning (24h later: test 1) and final test (7days later: test 2), in an active avoidance apparatus, to evaluate memory. Conditioned avoidance responses (CAR, % of 50 trials) were registered. In acquisition sessions, similar CAR were obtained among age matched animals from all strains. However, a significant decrease in CAR was observed throughout the aging process (3mo: 8.8+/-2.3%; 6mo: 4.1+/-0.6%; 12mo: 2.2+/-0.6%, 18mo: 3.6+/-0.6%, Pprocess. In test 1, as expected, memory retention increased significantly (Pmemory retention. In test 2, 3- and 6-month-old wt and koB1 mice of all ages showed a significant improvement in memory (Pmemory retention. We suggest that, during the aging process, the B1 receptor could be involved in neurodegeneration and memory loss. Nevertheless, the B2 receptor is apparently acting as a neuroprotective factor. Copyright 2009 Elsevier Ltd. All rights reserved.

Digestion of atopic allergens with trypsin α-chymotrypsin and pancreatic kallikrein, and influence of the allergens upon the proteolytic and esterolytic activity of these enzymes

NARCIS (Netherlands)

Berrens, L.

1968-01-01

The action of bovine trypsin, α-chymotrypsin and pancreatic kallikrein upon a number of atopic allergens has been studied by pH-stat measurements during short-term incubation. Most atopic allergens proved chemically resistant towards these enzymes. Graphs of enzyme susceptibility vs. the ratio of

A four-kallikrein panel for the prediction of repeat prostate biopsy: data from the European Randomized Study of Prostate Cancer screening in Rotterdam, Netherlands.

Science.gov (United States)

Gupta, A; Roobol, M J; Savage, C J; Peltola, M; Pettersson, K; Scardino, P T; Vickers, A J; Schröder, F H; Lilja, H

2010-08-24

Most men with elevated levels of prostate-specific antigen (PSA) do not have prostate cancer, leading to a large number of unnecessary biopsies. A statistical model based on a panel of four kallikreins has been shown to predict the outcome of a first prostate biopsy. In this study, we apply the model to an independent data set of men with previous negative biopsy but persistently elevated PSA. The study cohort consisted of 925 men with a previous negative prostate biopsy and elevated PSA (>or=3 ng ml(-1)), with 110 prostate cancers detected (12%). A previously published statistical model was applied, with recalibration to reflect the lower positive biopsy rates on rebiopsy. The full-kallikrein panel had higher discriminative accuracy than PSA and DRE alone, with area under the curve (AUC) improving from 0.58 (95% confidence interval (CI): 0.52, 0.64) to 0.68 (95% CI: 0.62, 0.74), Por=7) at biopsy with AUC improving from 0.76 (95% CI: 0.64, 0.89) to 0.87 (95% CI: 0.81, 0.94), P=0.003). Application of the panel to 1000 men with persistently elevated PSA after initial negative biopsy, at a 15% risk threshold would reduce the number of biopsies by 712; would miss (or delay) the diagnosis of 53 cancers, of which only 3 would be Gleason 7 and the rest Gleason 6 or less. Our data constitute an external validation of a previously published model. The four-kallikrein panel predicts the result of repeat prostate biopsy in men with elevated PSA while dramatically decreasing unnecessary biopsies.

Purification, structural characterization, and myotropic activity of a peptide related to des-Arg(9)-bradykinin from an elasmobranch fish, the little skate, Leucoraja erinacea.

Science.gov (United States)

Anderson, W Gary; Leprince, Jérôme; Conlon, J Michael

2008-08-01

A bradykinin (BK)-related peptide was isolated from heat-denaturated plasma from an elasmobranch fish, the little skate, Leucoraja erinacea after incubation with porcine pancreatic kallikrein. The primary structure of the peptide (H-Gly-Ile-Thr-Ser-Trp-Leu-Pro-Phe-OH; skate BK) shows limited structural similarity to the mammalian B1 receptor agonist, des-Arg(9)-BK. The myotropic activities of synthetic skate BK, and the analog skate [Arg(9)]BK, were examined in isolated skate vascular and intestinal smooth muscle preparations. Skate BK produced a concentration-dependent constriction of the mesenteric artery (EC(50)=4.37x10(-8)M; maximum response=103.4+/-10.23% of the response to 60mM KCl) but the response to skate [Arg(9)]BK was appreciably weaker (response to 10(-6)M=73.0+/-23.4% of the response to 60mM KCl). Neither the first branchial gill arch nor the ventral aorta responded to either purified peptide. Skate BK also produced a concentration-dependent constriction of intestinal smooth muscle preparations (EC(50)=2.74x10(-7)M; maximum response 31.0+/-12.2% of the response to 10(-5)M acetylcholine). Skate [Arg(9)]BK was without effect on the intestinal preparation. The data provide evidence for the existence of the kallikrein-kinin system in a phylogenetically ancient vertebrate group and the greater potency of skate BK compared with the analog skate [Arg(9)]BK suggests that the receptor mediating vascular responses resembles the mammalian B1 receptor more closely than the B2 receptor.

Sexual hormones modulate compensatory renal growth and function

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Pablo J. Azurmendi

2013-12-01

Full Text Available The role played by sexual hormones and vasoactive substances in the compensatory renal growth (CRG that follows uninephrectomy (uNx is still controversial. Intact and gonadectomized adult Wistar rats of both sexes, with and without uNx, performed at 90 days age, were studied at age 150 days. Daily urine volume, electrolyte excretion and kallikrein activity (UKa were determined. Afterwards, glomerular filtration rate and blood pressure were measured, the kidneys weighed and DNA, protein and RNA studied to determine nuclei content and cell size. When the remnant kidney weight at age 150 days was compared with the weight of the kidney removed at the time of uNx, male uNx rats showed the greatest CRG (50% while growth in the other uNx groups was 25%, 15% and 19% in orchidectomized, female and ovariectomized rats, respectively. The small CRG observed in the uNx female rats was accompanied by the lowest glomerular filtration value, 0.56 ± 0.02 ml/min/g kwt compared, with the other uNx groups, p < 0.05. Cell size (protein or RNA/DNA was similar for all the groups except for uNx orchidectomized rats. In this group the cytoplasmatic protein or RNA content was lower than in the other groups while DNA (nuclei content was similar. Some degree of hyperplasia was determined by DNA content in the uNx groups. Male sexual hormones positively influenced CRG and its absence modulated cell size. Female sexual hormones, instead, did not appear to stimulate CRG. The kallikrein kinin system may not be involved in CRG.

Transcriptome reveals the overexpression of a kallikrein gene cluster (KLK1/3/7/8/12) in the Tibetans with high altitude-associated polycythemia.

Science.gov (United States)

Li, Kang; Gesang, Luobu; Dan, Zeng; Gusang, Lamu

2017-02-01

High altitude-associated polycythemia (HAPC) is a very common disease. However, it the disease is still unmanageable and the related molecular mechanisms remain largely unclear. In the present study, we aimed to explore the molecular mechanisms responsible for the development of HAPC using transcriptome analysis. Transcriptome analysis was conducted in 3 pairs of gastric mucosa tissues from patients with HAPC and healthy residents at a similar altitude. Endoscopy and histopathological analyses were used to examine the injury to gastric tissues. Molecular remodeling was performed for the interaction between different KLK members and cholesterol. HAPC was found to lead to morphological changes and pathological damage to the gastric mucosa of patients. A total of 10,304 differentially expressed genes (DEGs) were identified. Among these genes, 4,941 DEGs were upregulated, while 5,363 DEGs were downregulated in the patients with HAPC (fold change ≥2, P17-fold. All the members had high-score binding cholesterol, particularly for the polymers of KLK7. The kallikrein gene cluster (KLK1/3/7/8/12) is on chromosome 19q13.3-13.4. The elevated levels of KLK1, KLK3, KLK7, KLK8 and KLK12 may be closely associated with the hypertension, inflammation, obesity and other gastric injuries associated with polycythemia. The interaction of KLKs and cholesterol maybe play an important role in the development of hypertension. The findings of the present study revealed that HAPC induces gastric injury by upregulating the kallikrein gene cluster (KLK1/3/7/8/12), which can bind cholesterol and result in kallikrein hypertension. These findings provide some basic information for understanding the molecular mechanisms responsible for HAPC and HAPC-related diseases.

Potentiation of the vascular response to kinins by inhibition of myocardial kininases.

Science.gov (United States)

Dendorfer, A; Wolfrum, S; Schäfer, U; Stewart, J M; Inamura, N; Dominiak, P

2000-01-01

Inhibitors of angiotensin I-converting enzyme (ACE) are very efficacious in the potentiation of the actions of bradykinin (BK) and are able to provoke a B(2) receptor-mediated vasodilation even after desensitization of this receptor. Because this activity cannot be easily explained only by an inhibition of kinin degradation, direct interactions of ACE inhibitors with the B(2) receptor or its signal transduction have been hypothesized. To clarify the significance of degradation-independent potentiation, we studied the vasodilatory effects of BK and 2 degradation-resistant B(2) receptor agonists in the isolated rat heart, a model in which ACE and aminopeptidase P (APP) contribute equally to the degradation of BK. Coronary vasodilation to BK and to a peptidic (B6014) and a nonpeptidic (FR190997) degradation-resistant B(2) agonist was assessed in the presence or absence of the ACE inhibitor ramiprilat, the APP inhibitor mercaptoethanol, or both. Ramiprilat or mercaptoethanol induced leftward shifts in the BK dose-response curve (EC(50)=3.4 nmol/L) by a factor of 4.6 or 4.9, respectively. Combined inhibition of ACE and APP reduced the EC(50) of BK to 0.18 nmol/L (ie, by a factor of 19) but potentiated the activity of B6014 (EC(50)=1.9 nmol/L) only weakly without altering that of FR190997 (EC(50)=0.34 nmol/L). Desensitization of B(2) receptors was induced by the administration of BK (0.2 micromol/L) or FR190997 (0.1 micromol/L) for 30 minutes; the vascular reactivity to ramiprilat or increasing doses of BK was tested thereafter. After desensitization with BK, but not FR190997, an additional application of ramiprilat provoked a B(2) receptor-mediated vasodilation. High BK concentrations were still effective at the desensitized receptor. The process of desensitization was not altered by ramiprilat. These results show that in this model, all potentiating actions of ACE inhibitors on kinin-induced vasodilation are exclusively related to the reduction in BK breakdown and are

3H-thymidine autoradiographic study of cell proliferation and the influence of isoproterenol and kallikrein in various cell populations of the gastrointestinal tract in animal experiments

International Nuclear Information System (INIS)

Albrecht, S.

1981-01-01

Morphological studies were carried out with the aim of studying cell proliferation in various tissues (stable and epithelial tissues) of the gastrointestinal tract. The cells were studied by 3 H thymidine autoradiography in the normal age cycle and under the influence of kallikrein or isoproterenol. Epithelial cells and smooth muscle cells of the forestomach, stomach, small intestine and colon were investigated and, in the case of the stomach, also connective-tissue cells of the mucotic stroma. Counts across the total epithelial thickness yielded similar results for the oesophagus and the forestomach. A count of 1000 cells per animal was found to yield representative information on a defined type of cell. Kallikrein was not found to have a constant mitosis-promoting effect. Isoproterenol caused the labelling index to increase or to decrease; in higher concentrations, it increased the proliferation rate in all cell types. In male animals, the labelling indices of connective-tissue cells of the gastric mucosa were significantly higher than in female animals. (orig./MG) [de

The renoprotective effect of angiotensin-converting enzyme inhibitors in experimental chronic renal failure is not dependent on enhanced kinin activity.

Science.gov (United States)

Nabokov, A; Amann, K; Gassmann, P; Schwarz, U; Orth, S R; Ritz, E

1998-01-01

Angiotensin-converting enzyme (ACE) inhibitors have been shown to ameliorate the progression of glomerulosclerosis both in experimental models of uraemia and in patients with renal failure. It has not been documented, however, whether this is due to a decrease in angiotensin II generation or is a consequence of elevated local level of bradykinin. Morphometric investigation of renal tissue was performed in 5/6 nephrectomized (SNx) rats, i.e. untreated or treated with the ACE inhibitor ramipril (SNx-RAM), the B2 kinin receptor antagonist HOE 140 (SNx-HOE), or a combination of both (SNx-RAM + HOE) over 8 weeks. A further group of SNx received delayed treatment with ramipril from week 5 onward (SNx-RAMD). In addition, a sham-operated (SHAM) control group was studied. Systolic blood pressure was significantly lower in both SNx-RAM and SNx-RAM + HOE groups compared to (untreated) SNx. The glomerulosclerosis index (GSI) was substantially higher in the (untreated) SNx group (0.24 +/- 0.04) vs SHAM (0.02 +/- 0.01). A significantly higher GSI was found in the SNx-HOE group (0.45 +/- 0.08) as compared to (untreated) SNx. However, in the SNx-RAM, SNx-RAM + HOE, and SNx-RAMD groups, the GSI was lowered to a similar extent (0.1 +/- 0.02, 0.09 +/- 0.02, and 0.07 +/- 0.01 respectively). In addition, a concomitant attenuation of tubulointerstitial damage was noted in all the above groups. Increased kinin activity does not appear to play a major role in the renoprotective effect of ACE inhibitors in the remnant kidney model.

Skin barrier homeostasis in atopic dermatitis: feedback regulation of kallikrein activity.

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Reiko J Tanaka

Full Text Available Atopic dermatitis (AD is a widely spread cutaneous chronic disease characterised by sensitive reactions (eg. eczema to normally innocuous elements. Although relatively little is understood about its underlying mechanisms due to its complexity, skin barrier dysfunction has been recognised as a key factor in the development of AD. Skin barrier homeostasis requires tight control of the activity of proteases, called kallikreins (KLKs, whose activity is regulated by a complex network of protein interactions that remains poorly understood despite its pathological importance. Characteristic symptoms of AD include the outbreak of inflammation triggered by external (eg. mechanical and chemical stimulus and the persistence and aggravation of inflammation even if the initial stimulus disappears. These characteristic symptoms, together with some experimental data, suggest the presence of positive feedback regulation for KLK activity by inflammatory signals. We developed simple mathematical models for the KLK activation system to study the effects of feedback loops and carried out bifurcation analysis to investigate the model behaviours corresponding to inflammation caused by external stimulus. The model analysis confirmed that the hypothesised core model mechanisms capture the essence of inflammation outbreak by a defective skin barrier. Our models predicted the outbreaks of inflammation at weaker stimulus and its longer persistence in AD patients compared to healthy control. We also proposed a novel quantitative indicator for inflammation level by applying principal component analysis to microarray data. The model analysis reproduced qualitative AD characteristics revealed by this indicator. Our results strongly implicate the presence and importance of feedback mechanisms in KLK activity regulation. We further proposed future experiments that may provide informative data to enhance the system-level understanding on the regulatory mechanisms of skin barrier

The Extreme Anterior Domain Is an Essential Craniofacial Organizer Acting through Kinin-Kallikrein Signaling

Czech Academy of Sciences Publication Activity Database

Jacox, L.; Šindelka, Radek; Chen, J.; Rothman, A.; Dickinson, A.; Sive, H.

2014-01-01

Roč. 8, č. 2 (2014), s. 595-608 ISSN 2211-1247 Institutional support: RVO:86652036 Keywords : CRANIAL NEURAL CREST * NITRIC-OXIDE SYNTHASE * XENOPUS-LAEVIS Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 8.358, year: 2014

The effects of nanomaterials on blood coagulation in hemostasis and thrombosis.

Science.gov (United States)

Simak, Jan; De Paoli, Silvia

2017-09-01

The blood coagulation balance in the organism is achieved by the interaction of the blood platelets (PLTs) with the plasma coagulation system (PCS) and the vascular endothelial cells. In healthy organism, these systems prevent thrombosis and, in events of vascular damage, enable blood clotting to stop bleeding. The dysregulation of hemostasis may cause serious thrombotic and/or hemorrhagic pathologies. Numerous engineered nanomaterials are being investigated for biomedical purposes and are unavoidably exposed to the blood. Also, nanomaterials may access vascular system after occupational, environmental, or other types of exposure. Thus, it is essential to evaluate the effects of engineered nanomaterials on hemostasis. This review focuses on investigations of nanomaterial interactions with the blood components involved in blood coagulation: the PCS and PLTs. Particular emphases include the pathophysiology of effects of nanomaterials on the PCS, including the kallikrein-kinin system, and on PLTs. Methods for investigating these interactions are briefly described, and a review of the most important studies on the interactions of nanomaterials with plasma coagulation and platelets is provided. WIREs Nanomed Nanobiotechnol 2017, 9:e1448. doi: 10.1002/wnan.1448 For further resources related to this article, please visit the WIREs website. © Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

Characterization of kallikrein-related peptidase 4 glycosylations.

Science.gov (United States)

Yamakoshi, Yasuo; Yamakoshi, Fumiko; Hu, Jan C-C; Simmer, James P

2011-12-01

Kallikrein-related peptidase 4 (KLK4) is a glycosylated serine protease that functions in the maturation (hardening) of dental enamel. Pig and mouse KLK4 contain three potential N-glycosylation sites. We isolated KLK4 from developing pig and mouse molars and characterized their N-glycosylations. N-glycans were enzymatically released by digestion with N-glycosidase F and fluorescently labeled with 2-aminobenzoic acid. Normal-phase high-performance liquid chromatography (NP-HPLC) revealed N-glycans with no, or with one, two, or three sialic acid attachments in pig KLK4 and with no, or with one or two sialic acid attachments in mouse KLK4. The labeled N-glycans were digested with sialidase to generate the asialo N-glycan cores that were fractionated by reverse-phase HPLC, and their retention times were compared with similarly labeled glycan standards. The purified cores were characterized by mass spectrometric and monosaccharide composition analyses. We determined that pig and mouse KLK4 have NA2 and NA2F biantennary N-glycan cores. The pig triantennary core is NA3. The mouse triantennary core is NA3 with a fucose connected by an α1-6 linkage, indicating that it is attached to the first N-acetyglucosamine (NA3F). We conclude that pig KLK4 has NA2, NA2F, and NA3 N-glycan cores with no, or with one, two, or three sialic acids. Mouse KLK4 has NA2, NA2F, and NA3F N-glycan cores with no, or with one or two sialic acids. © 2011 Eur J Oral Sci.

Rapid elimination kinetics of free PSA or human kallikrein-related peptidase 2 after initiation of gonadotropin-releasing hormone-antagonist treatment of prostate cancer

DEFF Research Database (Denmark)

Ulmert, David; Vickers, Andrew J; Scher, Howard I

2012-01-01

The utility of conventional prostate-specific antigen (PSA) measurements in blood for monitoring rapid responses to treatment for prostate cancer is limited because of its slow elimination rate. Prior studies have shown that free PSA (fPSA), intact PSA (iPSA) and human kallikrein-related peptidase...... of tPSA, fPSA, iPSA and hK2 after rapid induction of castration with degarelix (Firmagon(®)), a novel GnRH antagonist....

Analgesic Effect of Photobiomodulation on Bothrops Moojeni Venom-Induced Hyperalgesia: A Mechanism Dependent on Neuronal Inhibition, Cytokines and Kinin Receptors Modulation.

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Nikele Nadur-Andrade

2016-10-01

Full Text Available Envenoming induced by Bothrops snakebites is characterized by drastic local tissue damage that involves an intense inflammatory reaction and local hyperalgesia which are not neutralized by conventional antivenom treatment. Herein, the effectiveness of photobiomodulation to reduce inflammatory hyperalgesia induced by Bothrops moojeni venom (Bmv, as well as the mechanisms involved was investigated.Bmv (1 μg was injected through the intraplantar route in the right hind paw of mice. Mechanical hyperalgesia and allodynia were evaluated by von Frey filaments at different time points after venom injection. Low level laser therapy (LLLT was applied at the site of Bmv injection at wavelength of red 685 nm with energy density of 2.2 J/cm2 at 30 min and 3 h after venom inoculation. Neuronal activation in the dorsal horn spinal cord was determined by immunohistochemistry of Fos protein and the mRNA expression of IL-6, TNF-α, IL-10, B1 and B2 kinin receptors were evaluated by Real time-PCR 6 h after venom injection. Photobiomodulation reversed Bmv-induced mechanical hyperalgesia and allodynia and decreased Fos expression, induced by Bmv as well as the mRNA levels of IL-6, TNF-α and B1 and B2 kinin receptors. Finally, an increase on IL-10, was observed following LLLT.These data demonstrate that LLLT interferes with mechanisms involved in nociception and hyperalgesia and modulates Bmv-induced nociceptive signal. The use of photobiomodulation in reducing local pain induced by Bothropic venoms should be considered as a novel therapeutic tool for the treatment of local symptoms induced after bothropic snakebites.

Uşak İli Buğday Ekim Alanlarında Süne, [Eurygaster spp. (Hemiptera: Scutelleridae] Yumurtalarının Parazitlenme Oranları ile Buğday Tanelerindeki Emgi Oranları Arasındaki İlişkinin Belirlenmesi

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Erdal ZENGİN

2017-06-01

Full Text Available Bu çalışma, 2015-2016 yıllarında Uşak iline bağlı 10 köydeki Süne yumurtalarının parazitlenme oranlarının ve emgili tane sayılarının belirlenmesi ile bu oranlar arasındaki ilişkinin tespit edilmesi amacıyla yapılmıştır. Araştırma sonuçlarına göre, 2015 ve 2016 yıllarındaki en yüksek Süne yumurtası parazitlenme oranı ve emgili tane sayıları sırasıyla %95.4-%1.60, %90.7-%1.05 olarak bulunmuştur. Köylerde yapılan arazi çalışmaları sonucunda elde edilen oranlara çoklu karşılaştırma testi uygulanarak köyler arasındaki farklılıklar belirlenmiştir.  Parazitlenme oranı ile emgili tane sayısı arasında bir ilişkinin olup olmadığını belirlemek için her iki yıl verileri üzerinde yapılan regresyon analizi sonucunda, bu iki değişken arasında doğrusal bir ilişkinin olduğu tespit edilmiştir.

Novel kinin B1 receptor agonists with improved pharmacological profiles.

Science.gov (United States)

Côté, Jérôme; Savard, Martin; Bovenzi, Veronica; Bélanger, Simon; Morin, Josée; Neugebauer, Witold; Larouche, Annie; Dubuc, Céléna; Gobeil, Fernand

2009-04-01

There is some evidence to suggest that inducible kinin B1 receptors (B1R) may play beneficial and protecting roles in cardiovascular-related pathologies such as hypertension, diabetes, and ischemic organ diseases. Peptide B1R agonists bearing optimized pharmacological features (high potency, selectivity and stability toward proteolysis) hold promise as valuable therapeutic agents in the treatment of these diseases. In the present study, we used solid-phase methodology to synthesize a series of novel peptide analogues based on the sequence of Sar[dPhe(8)]desArg(9)-bradykinin, a relatively stable peptide agonist with moderate affinity for the human B1R. We evaluated the pharmacological properties of these peptides using (1) in vitro competitive binding experiments on recombinant human B1R and B2R (for index of selectivity determination) in transiently transfected human embryonic kidney 293 cells (HEK-293T cells), (2) ex vivo vasomotor assays on isolated human umbilical veins expressing endogenous human B1R, and (3) in vivo blood pressure tests using anesthetized lipopolysaccharide-immunostimulated rabbits. Key chemical modifications at the N-terminus, the positions 3 and 5 on Sar[dPhe(8)]desArg(9)-bradykinin led to potent analogues. For example, peptides 18 (SarLys[Hyp(3),Cha(5), dPhe(8)]desArg(9)-bradykinin) and 20 (SarLys[Hyp(3),Igl(5), dPhe(8)]desArg(9)-bradykinin) outperformed the parental molecule in terms of affinity, functional potency and duration of action in vitro and in vivo. These selective agonists should be valuable in future animal and human studies to investigate the potential benefits of B1R activation.

The link between high-fat meals and postprandial activation of blood coagulation factor VII possibly involves kallikrein

DEFF Research Database (Denmark)

Larsen, L F; Marckmann, P; Bladbjerg, Else-Marie

2000-01-01

Contrary to low-fat meals, high-fat meals are known to cause postprandial factor VII (FVII) activation, but the mechanism is unknown. To study the postprandial FVII activation in detail, 18 young men consumed in randomized order high-fat or low-fat test meals. Fasting and non-fasting blood samples...... that triglyceride-rich lipoproteins may activate prokallikrein. Neither plasma triglycerides nor kallikrein and activated FVII were statistically associated. This may suggest that additional factors are involved in the postprandial FVII activation. No clear evidence for a role of tissue factor expression...... by monocytes, factor XII or insulin in postprandial FVII activation was observed. Tissue factor pathway inhibitor and prothrombin fragment 1+2, a marker of thrombin generation, were not affected postprandially after either the high-fat or the low-fat meals. Our findings indicate that triglyceride...

Skin barrier disruption by sodium lauryl sulfate-exposure alters the expressions of involucrin, transglutaminase 1, profilaggrin, and kallikreins during the repair phase in human skin in vivo.

Science.gov (United States)

Törmä, Hans; Lindberg, Magnus; Berne, Berit

2008-05-01

Detergents are skin irritants affecting keratinocytes. In this study, healthy volunteers were exposed to water (vehicle) and 1% sodium lauryl sulfate (SLS) under occlusive patch tests for 24 hours. The messenger RNA (mRNA) expression of keratinocyte differentiation markers and of enzymes involved in corneodesmosome degradation was examined in skin biopsies (n=8) during the repair phase (6 hours to 7 days postexposure) using real-time reverse-transcription PCR. It was found that the expression of involucrin was increased at 6 hours, but then rapidly normalized. The expression of transglutaminase 1 exhibited a twofold increase after 24 hours in the SLS-exposed skin. Profilaggrin was decreased after 6 hours. Later (4-7 days), the expression in SLS-exposed areas was >50% above than in control areas. An increased and altered immunofluorescence pattern of involucrin, transglutaminase 1, and filaggrin was also found (n=4). At 6 hours post-SLS exposure, the mRNA expression of kallikrein-7 (KLK-7) and kallikrein-5 (KLK-5) was decreased by 50 and 75%, respectively, as compared with control and water-exposed areas. Thereafter, the expression pattern of KLK-7 and KLK-5 was normalized. Changes in protein expression of KLK-5 were also found. In conclusion, SLS-induced skin barrier defects induce altered mRNA expression of keratinocyte differentiation markers and enzymes degrading corneodesmosomes.

Design of the system of maintenance operations occupational safety and health database application of nuclear power station

International Nuclear Information System (INIS)

Wang Xuehong; Li Xiangyang; Ye Yongjun

2011-01-01

Based on the KKS code of building equipment in nuclear power station, this paper introduces the method of establishing the system of maintenance operation occupational safety and health database application. Through the application system of maintenance occupational safety and health database, it can summarize systematically all kinds of maintenance operation dangerous factor of nuclear power station, and make a convenience for staff to learn the maintenance operation dangerous factors and the prevention measures, so that it can achieve the management concept of 'precaution crucial, continuous improvement' that advocated by OSHMS. (authors)

Cellular localization of kinin B1 receptor in the spinal cord of streptozotocin-diabetic rats with a fluorescent [Nα-Bodipy]-des-Arg9-bradykinin

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Gaudreau Pierrette

2009-03-01

Full Text Available Abstract Background The kinin B1 receptor (B1R is upregulated by pro-inflammatory cytokines, bacterial endotoxins and hyperglycaemia-induced oxidative stress. In animal models of diabetes, it contributes to pain polyneuropathy. This study aims at defining the cellular localization of B1R in thoracic spinal cord of type 1 diabetic rats by confocal microscopy with the use of a fluorescent agonist, [Nα-Bodipy]-des-Arg9-BK (BdABK and selective antibodies. Methods Diabetes was induced by streptozotocin (STZ; 65 mg/kg, i.p.. Four days post-STZ treatment, B1R expression was confirmed by quantitative real-time PCR and autoradiography. The B1R selectivity of BdABK was determined by assessing its ability to displace B1R [125I]-HPP-desArg10-Hoe140 and B2R [125I]-HPP-Hoe 140 radioligands. The in vivo activity of BdABK was also evaluated on thermal hyperalgesia. Results B1R was increased by 18-fold (mRNA and 2.7-fold (binding sites in the thoracic spinal cord of STZ-treated rats when compared to control. BdABK failed to displace the B2R radioligand but displaced the B1R radioligand (IC50 = 5.3 nM. In comparison, IC50 values of B1R selective antagonist R-715 and B1R agonist des-Arg9-BK were 4.3 nM and 19 nM, respectively. Intraperitoneal BdABK and des-Arg9-BK elicited dose-dependent thermal hyperalgesia in STZ-treated rats but not in control rats. The B1R fluorescent agonist was co-localized with immunomarkers of microglia, astrocytes and sensory C fibers in the spinal cord of STZ-treated rats. Conclusion The induction and up-regulation of B1R in glial and sensory cells of the spinal cord in STZ-diabetic rats reinforce the idea that kinin B1R is an important target for drug development in pain processes.

Effect of 3-substituted 1,4-benzodiazepin-2-ones on maximal normalized rate of bradykinin-induced smooth muscle contraction in the presence of calcium channel blockers

Directory of Open Access Journals (Sweden)

P. A. Virych

2017-05-01

Full Text Available The development of modern organic chemistry and molecular modeling technologies simplify the search for potential inhibitors of various receptor systems and biological processes. The one of the directions is the development of analgesics of broad spectrum and low toxicity. It is important to search for inhibitors of the kinin-kallikrein system that regulates many functions: inflammation, pain, carcinogenesis, vascular tone, smooth muscle contraction and other. Derivatives of 3-substituted 1,4-benzodiazepine-2-ones have a unique spatial conformation that allows one to simulate β-structures of bioactive peptides. The functional activity of compounds is determined by properties of their peripheral chemical radicals. We analyzed the effect of 3-substituted 1,4-benzodiazepin-2-ones derivatives on the normalized maximal rate of bradykinin-induced smooth muscle contraction and relaxation of the stomach in the presence of calcium channel blockers: verapamil (1 μM, gadolinium (300 μM and 2-aminoethyl diphenylborinate (0.1 μM. The levels of bradykinin and 3-arylamino-1,2-dihydro-3H-1,4-benzodiazepine-2-ones in incubation solution were 10–6 M. Data processing on dynamics of contraction was performed according to the method of Burdyha and Kosterin. Compounds MX-1775 and MX-1925 reduced maximal normalized rate (Vn of bradykinin-induced smooth muscle contraction in the presence of Gd3+ by 21.2% and 31.0% respectively. Compound MX-1925 increased Vn of relaxation by 11.6%. A similar effect is typical for MX-2011, where there is an increase by 34.6%. In the presence of verapamil this compound additionally decreased Vn contraction by 20.5%. Substances MX-1775, MX-2004 and MX-1925 restored maximal normalized rate of relaxation to original values of bradykinin-induced contraction. In the presence of 2-aminoethyldiphenylborinate MX-1775 additionally reduced Vn of contractions by 7.5%. 3-substituted 1,4-benzo­diazepine-2-ones did not change the maximal

Hemşirelerin problem çözme becerileri ve atılganlıkları arasındaki ilişkinin incelenmesi

OpenAIRE

Polat, Hatice

2014-01-01

Araştırma, hemşirelerin problem çözme becerileri ile atılganlıkları arasındaki ilişkinin incelenmesi amacıyla analitik- kesitsel olarak planlanmıştır. Araştırmanın evrenini 2011 yılı itibariyle ve araştırma takvimi süresince Muğla ili Muğla Üniversitesi Eğitim ve Araştırma Hastanesi'nde çalışan 300 hemşire oluşturmaktadır. Araştırma verileri, tanımlayıcı özellikleri içeren Kişisel Bilgi Formu, Rathus Atılganlık Envanteri ve Gözden Geçirilmiş Sosyal Sorun Çözme Envanteri (GGSSÇE) ile toplanmış...

Bradykinin-induced lung inflammation and bronchoconstriction: role in parainfluenze-3 virus-induced inflammation and airway hyperreactivity.

Science.gov (United States)

Broadley, Kenneth J; Blair, Alan E; Kidd, Emma J; Bugert, Joachim J; Ford, William R

2010-12-01

Inhaled bradykinin causes bronchoconstriction in asthmatic subjects but not nonasthmatics. To date, animal studies with inhaled bradykinin have been performed only in anesthetized guinea pigs and rats, where it causes bronchoconstriction through sensory nerve pathways. In the present study, airway function was recorded in conscious guinea pigs by whole-body plethysmography. Inhaled bradykinin (1 mM, 20 s) caused bronchoconstriction and influx of inflammatory cells to the lungs, but only when the enzymatic breakdown of bradykinin by angiotensin-converting enzyme and neutral endopeptidase was inhibited by captopril (1 mg/kg i.p.) and phosphoramidon (10 mM, 20-min inhalation), respectively. The bronchoconstriction and cell influx were antagonized by the B(2) kinin receptor antagonist 4-(S)-amino-5-(4-{4-[2,4-dichloro-3-(2,4-dimethyl-8-quinolyloxymethyl)phenylsulfonamido]-tetrahydro-2H-4-pyranylcarbonyl}piperazino)-5-oxopentyl](trimethyl)ammonium chloride hydrochloride (MEN16132) when given by inhalation (1 and 10 μM, 20 min) and are therefore mediated via B(2) kinin receptors. However, neither intraperitioneal MEN16132 nor the peptide B(2) antagonist icatibant, by inhalation, antagonized these bradykinin responses. Sensitization of guinea pigs with ovalbumin was not sufficient to induce airway hyperreactivity (AHR) to the bronchoconstriction by inhaled bradykinin. However, ovalbumin challenge of sensitized guinea pigs caused AHR to bradykinin and histamine. Infection of guinea pigs by nasal instillation of parainfluenza-3 virus produced AHR to inhaled histamine and lung influx of inflammatory cells. These responses were attenuated by the bradykinin B(2) receptor antagonist MEN16132 and H-(4-chloro)DPhe-2'(1-naphthylalanine)-(3-aminopropyl)guanidine (VA999024), an inhibitor of tissue kallikrein, the enzyme responsible for lung synthesis of bradykinin. These results suggest that bradykinin is involved in virus-induced inflammatory cell influx and AHR.

Kallikrein-related peptidase 7 is a potential target for the treatment of pancreatic cancer

Science.gov (United States)

Zheng, Jun; Zhang, Ding; Liu, Wei; Zheng, Wei Hong; Li, Xiao Song; Yao, Ru Cheng; Wang, Fangyu; Liu, Sen; Tan, Xiao

2018-01-01

Pancreatic cancer is one of the deadliest cancers with very poor prognosis, and the five-year survival rate of the patients is less than 5% after diagnosis. Kallikrein-related peptidases (KLKs) belong to a serine protease family with 15 members that play important roles in cellular physiological behavior and diseases. The high expression level of KLK7 in pancreatic cancer tissues is considered to be a marker for the poor prognosis of this disease. In this work, we set out to investigate whether KLK7 could be a target for the treatment of pancreatic cancer. Short hairpin RNAs (shRNAs) were designed and constructed in lentivirus to knock down KLK7 in pancreatic cancer cell line PANC-1, and the real time cellular analysis (RTCA) was used to evaluate cell proliferation, migration and invasion abilities. Small molecules inhibiting KLK7 were discovered by computer-aided drug screening and used to inhibit PANC-1 cells. Our results confirmed that KLK7 is significantly up-regulated in pancreatic cancer tissue, and knocking down or inhibiting KLK7 efficiently inhibited the proliferation, migration and invasion of pancreatic cancer cells. This study suggested that KLK7 could be a potential chemotherapy target for treatment of pancreatic cancer, which would provide us a novel strategy for the treatment of this disease. PMID:29560118

Kallikrein-related peptidase 4 induces cancer-associated fibroblast features in prostate-derived stromal cells.

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Kryza, Thomas; Silva, Lakmali M; Bock, Nathalie; Fuhrman-Luck, Ruth A; Stephens, Carson R; Gao, Jin; Samaratunga, Hema; Lawrence, Mitchell G; Hooper, John D; Dong, Ying; Risbridger, Gail P; Clements, Judith A

2017-10-01

The reciprocal communication between cancer cells and their microenvironment is critical in cancer progression. Although involvement of cancer-associated fibroblasts (CAF) in cancer progression is long established, the molecular mechanisms leading to differentiation of CAFs from normal fibroblasts are poorly understood. Here, we report that kallikrein-related peptidase-4 (KLK4) promotes CAF differentiation. KLK4 is highly expressed in prostate epithelial cells of premalignant (prostatic intraepithelial neoplasia) and malignant lesions compared to normal prostate epithelia, especially at the peristromal interface. KLK4 induced CAF-like features in the prostate-derived WPMY1 normal stromal cell line, including increased expression of alpha-smooth muscle actin, ESR1 and SFRP1. KLK4 activated protease-activated receptor-1 in WPMY1 cells increasing expression of several factors (FGF1, TAGLN, LOX, IL8, VEGFA) involved in prostate cancer progression. In addition, KLK4 induced WPMY1 cell proliferation and secretome changes, which in turn stimulated HUVEC cell proliferation that could be blocked by a VEGFA antibody. Importantly, the genes dysregulated by KLK4 treatment of WPMY1 cells were also differentially expressed between patient-derived CAFs compared to matched nonmalignant fibroblasts and were further increased by KLK4 treatment. Taken together, we propose that epithelial-derived KLK4 promotes tumour progression by actively promoting CAF differentiation in the prostate stromal microenvironment. © 2017 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.

Comparison of gene expression of mitogenic kinin path in adherent and non-adherent CD 34-stem cells using oligonucleotide microarrays.

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Krzysztof Machaj

2008-02-01

Full Text Available One of the more interesting cells present in the umbilical cord blood - as far as their potential clinical use is concerned - are stem cells not presenting the CD34 antigen. These are the pluripotential cells with their biological properties similar to mesenchymal stem cells, with the ability to differentiate into such tissue types as bone, cartilage, nervous (to some extent, glia and muscle. The authors compared the activity of genes coding the proteins in mitogenic signal paths activated by kinin receptors using oligonucleotide microarrays in adherent and non-adherent CD 34- cells derived from umbilical cord blood. In the linear regression model with a 95% prognosis area for differentiating genes outside this area, the following genes were selected: c-jun (present in 3 isoforms and c-fos. The fos and jun genes create the AP-1 transcriptive factor which regulates the expression of genes taking part in numerous cellular processes, including the cell cycle and mitosis. The obtained results shed some light on the molecular processes behind the MSC proliferation and are a starting point for further studies on the mesenchymal stem cell biology.

Desmoglein 2 is a substrate of kallikrein 7 in pancreatic cancer

International Nuclear Information System (INIS)

Ramani, Vishnu C; Hennings, Leah; Haun, Randy S

2008-01-01

In a previous report we have demonstrated that the chymotryptic-like serine protease kallikrein 7 (KLK7/hK7) is overexpressed in pancreatic cancer. In normal skin, hK7 is thought to participate in skin desquamation by contributing in the degradation of desmosomal components, such as desmogleins. Thus, the ability of hK7 to degrade desmogleins was assessed and the effect of hK7 expression on desmoglein 2 was examined in cultured pancreatic cancer cells. The expression of Dsg1, Dsg2, and Dsg3 in pancreatic tissues was examined by immunohistochemistry and their expression in two pancreatic cancer cell lines, BxPC-3 and Panc-1, was determined by western blot analysis. The ability of hK7 to degrade Dsg1 and Dsg2 was investigated using in vitro degradation assays. BxPC-3 cells stably transfected to overexpress hK7 were used to examine the effect of hK7 on cell-surface resident Dsg2. The levels of immunoreactive Dsg1 and Dsg2 were reduced in pancreatic adenocarcinomas compared with both normal pancreatic and chronic pancreatitis tissues. Among the desmosomal proteins examined, Dsg2 exhibited robust expression on the surface of BxPC-3 cells. When hK7 was overexpressed in this cell line, there was a significant increase in the amount of soluble Dsg2 released into the culture medium compared with vector-transfected control cells. A reduction in the amount of the cell adhesion components Dsg1 and Dsg2 in pancreatic tumors suggests that loss of these desmosomal proteins may play a role in pancreatic cancer invasion. Using in vitro degradation assays, both Dsg1 and Dsg2 could be readily proteolyzed by hK7, which is overexpressed in pancreatic adenocarcinomas. The enforced expression of hK7 in BxPC-3 cells that express significant amounts of Dsg2 resulted in a marked increase in the shedding of soluble Dsg2, which is consistent with the notion that aberrant expression of hK7 in pancreatic tumors may result in diminished cell-cell adhesion and facilitate tumor cell invasion

Twins born in different environments? Nuclei of two dSphs: isolated galaxy KKS3 and ESO269-66, a close neighbor of NGC5128

Science.gov (United States)

Sharina, Margarita; Karachentsev, Igor; Kniazev, Alexei

2015-08-01

The close vicinity of giant neighbors determines the environmental mechanisms that have been considered responsible for the evolution of dwarf spheroidal galaxies (dSphs). In the recent years, Karachentsev and collaborators have reported on the discovery of a few truly isolated dSphs in the Local volume. This study focuses on one of these unusual objects, KKs3 (MV=-12.3 mag). It contains a massive globular cluster (GC) (MV=-8.5 mag) near its optical center. We have performed the estimation of its radial velocity using a medium-resolution spectrum obtained with the RSS spectrograph at the Southern African Large Telescope (SALT). The signal-to-noise ratio in the spectrum was sufficient to estimate the age and metallicity for the GC using simple stellar population models, and the methods of full spectrum fitting and Lick index diagnostic diagrams. The results contribute to the knowledge about the origin of massive star clusters and their host dSphs.In the same way we have analyzed another luminous GC (MV=-10) in the center of ESO269-66 (MB=-15.4), a close dSph neighbor of the giant S0 Cen A. The cluster was observed with SALT in the same instrumental configuration. The structure and star formation histories of the two galaxies look rather similar. Both of them have experienced several star-forming events. The most recent ones occurred 1÷2 Gyr ago, and most powerful bursts happened 12÷14 Gyrs ago. Our analysis has shown that both GCs appear to be 1÷2 Gyr younger and 0.2÷0.3 dex more metal-rich than the most ancient metal-poor stars in the host dSphs. We examine signatures of multiple stellar population in the GCs using out data. Since central star-forming bursts were extended in time, the massive clusters might be considered as nuclei of the galaxies.

Factor XII-independent activation of the bradykinin-forming cascade

DEFF Research Database (Denmark)

Joseph, Kusumam; Tholanikunnel, Baby G; Bygum, Anette

2013-01-01

and assayed for kallikrein formation. C1-INH was removed from factor XII-deficient plasma by means of immunoadsorption. RESULTS: We demonstrate that prekallikrein-HK will activate to kallikrein in phosphate-containing buffers and that the rate is further accelerated on addition of heat shock protein 90...... the prekallikrein-HK complex to prevent HK cleavage either by prekallikrein or by prekallikrein-HK autoactivation to generate kallikrein. In patients with hereditary angioedema, kallikrein and bradykinin formation can occur without invoking factor XII activation, although the kallikrein formed can rapidly activate...

The Plant-Derived Bauhinia bauhinioides Kallikrein Proteinase Inhibitor (rBbKI Attenuates Elastase-Induced Emphysema in Mice

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Bruno Tadeu Martins-Olivera

2016-01-01

Full Text Available Background. Elastase mediates important oxidative actions during the development of chronic obstructive pulmonary disease (COPD. However, few resources for the inhibition of elastase have been investigated. Our study evaluated the ability of the recombinant plant derived Bauhinia bauhinioides Kallikrein proteinase Inhibitor (rBbKI to modulate elastase-induced pulmonary inflammation. Methods. C57Bl/6 mice were given intratracheal elastase (ELA group or saline (SAL group and were treated intraperitoneally with rBbKI (ELA-rBbKI and SAL-rBbKI groups. At day 28, the following analyses were performed: (I lung mechanics, (II exhaled nitric oxide (ENO, (III bronchoalveolar lavage fluid (BALF, and (IV lung immunohistochemical staining. Results. In addition to decreasing mechanical alterations and alveolar septum disruption, rBbKI reduced the number of cells in the BALF and decreased the cellular expression of TNF-α, MMP-9, MMP-12, TIMP-1, eNOS, and iNOS in airways and alveolar walls compared with the ELA group. rBbKI decreased the volume proportion of 8-iso-PGF2α, collagen, and elastic fibers in the airways and alveolar walls compared with the ELA group. A reduction in the number of MUC-5-positive cells in the airway walls was also observed. Conclusion. rBbKI reduced elastase-induced pulmonary inflammation and extracellular matrix remodeling. rBbKI may be a potential pharmacological tool for COPD treatment.

A refined model of the genomic basis for phenotypic variation in vertebrate hemostasis.

Science.gov (United States)

Ribeiro, Ângela M; Zepeda-Mendoza, M Lisandra; Bertelsen, Mads F; Kristensen, Annemarie T; Jarvis, Erich D; Gilbert, M Thomas P; da Fonseca, Rute R

2015-06-30

Hemostasis is a defense mechanism that enhances an organism's survival by minimizing blood loss upon vascular injury. In vertebrates, hemostasis has been evolving with the cardio-vascular and hemodynamic systems over the last 450 million years. Birds and mammals have very similar vascular and hemodynamic systems, thus the mechanism that blocks ruptures in the vasculature is expected to be the same. However, the speed of the process varies across vertebrates, and is particularly slow for birds. Understanding the differences in the hemostasis pathway between birds and mammals, and placing them in perspective to other vertebrates may provide clues to the genetic contribution to variation in blood clotting phenotype in vertebrates. We compiled genomic data corresponding to key elements involved in hemostasis across vertebrates to investigate its genetic basis and understand how it affects fitness. We found that: i) fewer genes are involved in hemostasis in birds compared to mammals; and ii) the largest differences concern platelet membrane receptors and components from the kallikrein-kinin system. We propose that lack of the cytoplasmic domain of the GPIb receptor subunit alpha could be a strong contributor to the prolonged bleeding phenotype in birds. Combined analysis of laboratory assessments of avian hemostasis with the first avian phylogeny based on genomic-scale data revealed that differences in hemostasis within birds are not explained by phylogenetic relationships, but more so by genetic variation underlying components of the hemostatic process, suggestive of natural selection. This work adds to our understanding of the evolution of hemostasis in vertebrates. The overlap with the inflammation, complement and renin-angiotensin (blood pressure regulation) pathways is a potential driver of rapid molecular evolution in the hemostasis network. Comparisons between avian species and mammals allowed us to hypothesize that the observed mammalian innovations might have

SwissProt search result: AK061101 [KOME

Lifescience Database Archive (English)

Full Text Available AK061101 006-207-A12 (P14272) Plasma kallikrein precursor (EC 3.4.21.34) (Plasma prekallikrein...) (Kininogenin) (Fletcher factor) [Contains: Plasma kallikrein heavy chain; Plasma kallikrein light chain] KLKB1_RAT 7e-33 ...

SwissProt search result: AK112119 [KOME

Lifescience Database Archive (English)

Full Text Available AK112119 006-303-H09 (P03952) Plasma kallikrein precursor (EC 3.4.21.34) (Plasma prekallikrein...) (Kininogenin) (Fletcher factor) [Contains: Plasma kallikrein heavy chain; Plasma kallikrein light chain] KLKB1_HUMAN 2e-21 ...

SwissProt search result: AK112005 [KOME

Lifescience Database Archive (English)

Full Text Available AK112005 006-202-F10 (P03952) Plasma kallikrein precursor (EC 3.4.21.34) (Plasma prekallikrein...) (Kininogenin) (Fletcher factor) [Contains: Plasma kallikrein heavy chain; Plasma kallikrein light chain] KLKB1_HUMAN 5e-21 ...

SwissProt search result: AK061101 [KOME

Lifescience Database Archive (English)

Full Text Available AK061101 006-207-A12 (P26262) Plasma kallikrein precursor (EC 3.4.21.34) (Plasma prekallikrein...) (Kininogenin) (Fletcher factor) [Contains: Plasma kallikrein heavy chain; Plasma kallikrein light chain] KLKB1_MOUSE 3e-34 ...

SwissProt search result: AK109059 [KOME

Lifescience Database Archive (English)

Full Text Available AK109059 002-154-F02 (P26262) Plasma kallikrein precursor (EC 3.4.21.34) (Plasma prekallikrein...) (Kininogenin) (Fletcher factor) [Contains: Plasma kallikrein heavy chain; Plasma kallikrein light chain] KLKB1_MOUSE 8e-27 ...

SwissProt search result: AK112119 [KOME

Lifescience Database Archive (English)

Full Text Available AK112119 006-303-H09 (P26262) Plasma kallikrein precursor (EC 3.4.21.34) (Plasma prekallikrein...) (Kininogenin) (Fletcher factor) [Contains: Plasma kallikrein heavy chain; Plasma kallikrein light chain] KLKB1_MOUSE 3e-25 ...

SwissProt search result: AK112119 [KOME

Lifescience Database Archive (English)

Full Text Available AK112119 006-303-H09 (P14272) Plasma kallikrein precursor (EC 3.4.21.34) (Plasma prekallikrein...) (Kininogenin) (Fletcher factor) [Contains: Plasma kallikrein heavy chain; Plasma kallikrein light chain] KLKB1_RAT 8e-24 ...

SwissProt search result: AK109059 [KOME

Lifescience Database Archive (English)

Full Text Available AK109059 002-154-F02 (P14272) Plasma kallikrein precursor (EC 3.4.21.34) (Plasma prekallikrein...) (Kininogenin) (Fletcher factor) [Contains: Plasma kallikrein heavy chain; Plasma kallikrein light chain] KLKB1_RAT 1e-26 ...

SwissProt search result: AK061101 [KOME

Lifescience Database Archive (English)

Full Text Available AK061101 006-207-A12 (P03952) Plasma kallikrein precursor (EC 3.4.21.34) (Plasma prekallikrein...) (Kininogenin) (Fletcher factor) [Contains: Plasma kallikrein heavy chain; Plasma kallikrein light chain] KLKB1_HUMAN 4e-37 ...

New Therapeutic Approaches in Diabetic Retinopathy

Science.gov (United States)

Vaziri, Kamyar; Schwartz, Stephen G.; Relhan, Nidhi; Kishor, Krishna S.; Flynn Jr, Harry W.

2015-01-01

Diabetic retinopathy is a common microvascular complication of diabetes mellitus. It affects a substantial proportion of US adults over age 40. The condition is a leading cause of visual loss. Much attention has been given to expanding the role of current treatments along with investigating various novel therapies and drug delivery methods. In the treatment of diabetic macular edema (DME), intravitreal pharmacotherapies, especially anti-vascular endothelial growth factor (anti-VEGF) agents, have gained popularity. Currently, anti-VEGF agents are often used as first-line agents in center-involved DME, with recent data suggesting that among these agents, aflibercept leads to better visual outcomes in patients with worse baseline visual acuities. While photocoagulation remains the standard treatment for proliferative diabetic retinopathy (PDR), recent FDA approvals of ranibizumab and aflibercept in the management of diabetic retinopathy associated with DME may suggest a potential for pharmacologic treatments of PDR as well. Novel therapies, including small interfering RNAs, chemokines, kallikrein-kinin inhibitors, and various anti-angiogenic agents, are currently being evaluated for the management of diabetic retinopathy and DME. In addition to these strategies, novel drug delivery methods such as sustained-release implants and refillable reservoir implants are either under active evaluation or have recently gained FDA approval. This review provides an update on the novel developments in the treatment of diabetic retinopathy. PMID:26676668

Factor XI Deficiency Alters the Cytokine Response and Activation of Contact Proteases during Polymicrobial Sepsis in Mice.

Directory of Open Access Journals (Sweden)

Charles E Bane

Full Text Available Sepsis, a systemic inflammatory response to infection, is often accompanied by abnormalities of blood coagulation. Prior work with a mouse model of sepsis induced by cecal ligation and puncture (CLP suggested that the protease factor XIa contributed to disseminated intravascular coagulation (DIC and to the cytokine response during sepsis. We investigated the importance of factor XI to cytokine and coagulation responses during the first 24 hours after CLP. Compared to wild type littermates, factor XI-deficient (FXI-/- mice had a survival advantage after CLP, with smaller increases in plasma levels of TNF-α and IL-10 and delayed IL-1β and IL-6 responses. Plasma levels of serum amyloid P, an acute phase protein, were increased in wild type mice 24 hours post-CLP, but not in FXI-/- mice, supporting the impression of a reduced inflammatory response in the absence of factor XI. Surprisingly, there was little evidence of DIC in mice of either genotype. Plasma levels of the contact factors factor XII and prekallikrein were reduced in WT mice after CLP, consistent with induction of contact activation. However, factor XII and PK levels were not reduced in FXI-/- animals, indicating factor XI deficiency blunted contact activation. Intravenous infusion of polyphosphate into WT mice also induced changes in factor XII, but had much less effect in FXI deficient mice. In vitro analysis revealed that factor XIa activates factor XII, and that this reaction is enhanced by polyanions such polyphosphate and nucleic acids. These data suggest that factor XI deficiency confers a survival advantage in the CLP sepsis model by altering the cytokine response to infection and blunting activation of the contact (kallikrein-kinin system. The findings support the hypothesis that factor XI functions as a bidirectional interface between contact activation and thrombin generation, allowing the two processes to influence each other.

Identification of B cell recognized linear epitopes in a snake venom serine proteinase from the central American bushmaster Lachesis stenophrys.

Science.gov (United States)

Madrigal, M; Alape-Girón, A; Barboza-Arguedas, E; Aguilar-Ulloa, W; Flores-Díaz, M

2017-12-15

Snake venom serine proteinases are toxins that perturb hemostasis acting on proteins from the blood coagulation cascade, the fibrinolytic or the kallikrein-kinin system. Despite the relevance of these enzymes in envenomations by viper bites, the characterization of the antibody response to these toxins at the molecular level has not been previously addressed. In this work surface-located B cell recognized linear epitopes from a Lachesis stenophrys venom serine proteinase (UniProt accession number Q072L7) were predicted using an artificial neuronal network at the ABCpred server, the corresponding peptides were synthesized and their immunoreactivity was analyzed against a panel of experimental and therapeutic antivenoms. A molecular model of the L. stenophrys enzyme was built using as a template the structure of the D. acutus Dav-PA serine proteinase (Q9I8X1), which displays the highest degree of sequence similarity to the L. stenophrys enzyme among proteins of known 3D structure, and the surface-located epitopes were identified in the protein model using iCn3D. A total of 13 peptides corresponding to the surface exposed predicted epitopes from L. stenophrys serine proteinase were synthesized and, their reactivity with a rabbit antiserum against the recombinant enzyme and a panel of antivenoms was evaluated by a capture ELISA. Some of the epitopes recognized by monospecific and polyspecific antivenoms comprise sequences overlapping motifs conserved in viper venom serine proteinases. The identification and characterization of relevant epitopes recognized by B cells in snake venom toxins may provide valuable information for the preparation of immunogens that help in the production of improved therapeutic antivenoms. Copyright © 2017 Elsevier Ltd. All rights reserved.

Tissue kallikrein protects neurons from hypoxia/reoxygenation-induced cell injury through Homer1b/c.

Science.gov (United States)

Su, Jingjing; Tang, Yuping; Zhou, Houguang; Liu, Ling; Dong, Qiang

2012-11-01

Previous studies have demonstrated that human tissue kallikrein (TK) gene delivery protects against mouse cerebral ischemia/reperfusion (I/R) injury through bradykinin B2 receptor (B2R) activation. We have also reported that exogenous TK administration can suppress glutamate- or acidosis-induced neurotoxicity through the extracellular signal-regulated kinase1/2 (ERK1/2) pathway. To further explore the neuroprotection mechanisms of TK, in the present study we performed immunoprecipitation analysis and identified a scaffolding protein Homer1b/c using MALDI-TOF MS analysis. Here, we tested the hypothesis that TK reduces cell injury induced by oxygen and glucose deprivation/reoxygenation (OGD/R) through activating Homer1b/c. We found that TK increased the expression of Homer1b/c in a concentration- and time-dependent manner. Moreover, TK facilitated the translocation of Homer1b/c to the plasma membrane under OGD/R condition by confocal microscope assays. We also observed that overexpression of Homer1b/c showed the neuroprotection against OGD/R-induced cell injury by enhancing cell survival, reducing LDH release, caspase-3 activity and cell apoptosis. However, the knockdown of Homer1b/c by small interfering RNA showed the opposite effects, indicating that Homer1b/c had protective effects against OGD/R-induced neuronal injury. More interestingly, TK exerted its much more significantly neuroprotective effects after Homer1b/c overexpression, whereas it exerted its reduced effects after Homer1b/c knockdown. In addition, TK pretreatment increased the phosphorylation of the ERK1/2 and Akt-GSK3β through Homer1b/c activation. The beneficial effects of Homer1b/c were abolished by the ERK1/2 or PI3K antagonist. Therefore, we propose novel signaling mechanisms involved in the anti-hypoxic function of TK through activation of Homer1b/c-ERK1/2 and Homer1b/c-PI3K-Akt signaling pathways. Copyright © 2012 Elsevier Inc. All rights reserved.

Farklılıkların Yönetimi ile Öğrenen Okul Arasındaki İlişkinin Öğretmen Algılarına Göre İncelenmesi

OpenAIRE

DOĞAN, Soner; UĞURLU, Celal Teyyar; TOPÇU, İhsan; YİĞİT, Yakup

2018-01-01

Araştırmanın amacı, öğretmenlerin farklılıkların yönetimi ile öğrenen okul algılarını belirlemek ve farklılıkların yönetimi ile öğrenen okul arasındaki ilişkinin düzeyini saptamaktır. Bu çerçevede araştırma, ilişkisel tarama modelinde desenlenmiştir. Araştırmanın çalışma grubunu Sivas iline Bağlı Zara ilçesinde ilk, ortaokul ve lise düzeyinde toplam 18 okulda görev yapan 161 öğretmen oluşturmaktadır. Araştırma verileri öğrenen okul ölçeği (ÖOÖ) ve farklılıkların yönetimi ölçeği (FYÖ) aracılığ...

Fasitibant chloride, a kinin B2 receptor antagonist, and dexamethasone interact to inhibit carrageenan-induced inflammatory arthritis in rats

Science.gov (United States)

Valenti, Claudio; Giuliani, Sandro; Cialdai, Cecilia; Tramontana, Manuela; Maggi, Carlo Alberto

2012-01-01

BACKGROUND AND PURPOSE Bradykinin, through the kinin B2 receptor, is involved in inflammatory processes related to arthropathies. B2 receptor antagonists inhibited carrageenan-induced arthritis in rats in synergy with anti-inflammatory steroids. The mechanism(s) underlying this drug interaction was investigated. EXPERIMENTAL APPROACH Drugs inhibiting inflammatory mediators released by carrageenan were injected, alone or in combination, into the knee joint of pentobarbital anaesthetized rats 30 min before intra-articular administration of carrageenan. Their effects on the carrageenan-induced inflammatory responses (joint pain, oedema and neutrophil recruitment) and release of inflammatory mediators (prostaglandins, IL-1β, IL-6 and the chemokine GRO/CINC-1), were assessed after 6 h. KEY RESULTS The combination of fasitibant chloride (MEN16132) and dexamethasone was more effective than each drug administered alone in inhibiting knee joint inflammation and release of inflammatory mediators. Fasitibant chloride, MK571, atenolol, des-Arg9-[Leu8]-bradykinin (B2 receptor, leukotriene, catecholamine and B1 receptor antagonists, respectively) and dexketoprofen (COX inhibitor), reduced joint pain and, except for the latter, also diminished joint oedema. A combination of drugs inhibiting joint pain (fasitibant chloride, des-Arg9-[Leu8]-bradykinin, dexketoprofen, MK571 and atenolol) and oedema (fasitibant chloride, des-Arg9-[Leu8]-bradykinin, MK571 and atenolol) abolished the respective inflammatory response, producing inhibition comparable with that achieved with the combination of fasitibant chloride and dexamethasone. MK571 alone was able to block neutrophil recruitment. CONCLUSIONS AND IMPLICATIONS Bradykinin-mediated inflammatory responses to intra-articular carrageenan were not controlled by steroids, which were not capable of preventing bradykinin effects either by direct activation of the B2 receptor, or through the indirect effects mediated by release of eicosanoids

Smart CCP. Integration of CCP data in the existing infrastructure of a grid operator; Smart KKS. Integration von KKS-Daten in die bestehende Infrastruktur eines Netzbetreibers

Energy Technology Data Exchange (ETDEWEB)

Deiss, Rainer [EnBW Regional AG, Stuttgart (Germany); Mueller, Matthias [RBS wave GmbH, Stuttgart (Germany)

2012-07-01

The ever growing importance of the cathodic corrosion protection (CCP) requires a much greater integration of the CCP data in the existing infrastructure of a grid operator. The necessary technical adjustments to CCP current protection devices and CCP remote monitoring systems easily can be done with the help of embedded systems.

Blocking the proliferation of human tumor cell lines by peptidase inhibitors from Bauhinia seeds.

Science.gov (United States)

Nakahata, Adriana Miti; Mayer, Barbara; Neth, Peter; Hansen, Daiane; Sampaio, Misako Uemura; Oliva, Maria Luiza Vilela

2013-03-01

In cancer tumors, growth, invasion, and formation of metastasis at a secondary site play a pivotal role, participating in diverse processes in the development of the pathology, such as degradation of extracellular matrix. Bauhinia seeds contain relatively large quantities of peptidase inhibitors, and two Bauhinia inhibitors were obtained in a recombinant form from the Bauhinia bauhinioides species, B. bauhinoides cruzipain inhibitor, which is a cysteine and serine peptidase inhibitor, and B. bauhinioides kallikrein inhibitor, which is a serine peptidase inhibitor. While recombinant B. bauhinoides cruzipain inhibitor inhibits human neutrophil elastase cathepsin G and the cysteine proteinase cathepsin L, recombinant B. bauhinioides kallikrein inhibitor inhibits plasma kallikrein and plasmin. The effects of recombinant B. bauhinoides cruzipain inhibitor and recombinant B. bauhinioides kallikrein inhibitor on the viability of tumor cell lines with a distinct potential of growth from the same tissue were compared to those of the clinical cytotoxic drug 5-fluorouracil. At 12.5 µM concentration, recombinant B. bauhinoides cruzipain inhibitor and recombinant B. bauhinioides kallikrein inhibitor were more efficient than 5-fluorouracil in inhibiting MKN-28 and Hs746T (gastric), HCT116 and HT29 (colorectal), SkBr-3 and MCF-7 (breast), and THP-1 and K562 (leukemia) cell lines. Additionally, recombinant B. bauhinoides cruzipain inhibitor inhibited 40 % of the migration of Hs746T, the most invasive gastric cell line, while recombinant B. bauhinioides kallikrein inhibitor did not affect cell migration. Recombinant B. bauhinioides kallikrein inhibitor and recombinant B. bauhinoides cruzipain inhibitor, even at high doses, did not affect hMSC proliferation while 5-fluorouracil greatly reduced the proliferation rates of hMSCs. Therefore, both recombinant B. bauhinoides cruzipain inhibitor and recombinant B. bauhinioides kallikrein inhibitor might be considered for further studies

Activation of TRPV1 by capsaicin induces functional Kinin B1 receptor in rat spinal cord microglia

Directory of Open Access Journals (Sweden)

Talbot Sébastien

2012-01-01

Full Text Available Abstract Background The kinin B1 receptor (B1R is upregulated by pro-inflammatory cytokines and oxydative stress, which are enhanced by transient receptor potential vanilloid subtype 1 (TRPV1 activation. To examine the link between TRPV1 and B1R in inflammatory pain, this study aimed to determine the ability of TRPV1 to regulate microglial B1R expression in the spinal cord dorsal horn, and the underlying mechanism. Methods B1R expression (mRNA, protein and binding sites was measured in cervical, thoracic and lumbar spinal cord in response to TRPV1 activation by systemic capsaicin (1-50 mg/kg, s.c in rats pre-treated with TRPV1 antagonists (capsazepine or SB-366791, the antioxidant N-acetyl-L-cysteine (NAC, or vehicle. B1R function was assessed using a tail-flick test after intrathecal (i.t. injection of a selective B1R agonist (des-Arg9-BK, and its microglial localization was investigated by confocal microscopy with the selective fluorescent B1R agonist, [Nα-bodipy]-des-Arg9-BK. The effect of i.t. capsaicin (1 μg/site was also investigated. Results Capsaicin (10 to 50 mg/kg, s.c. enhanced time-dependently (0-24h B1R mRNA levels in the lumbar spinal cord; this effect was prevented by capsazepine (10 mg/kg, i.p.; 10 μg/site, i.t. and SB-366791 (1 mg/kg, i.p.; 30 μg/site, i.t.. Increases of B1R mRNA were correlated with IL-1β mRNA levels, and they were significantly less in cervical and thoracic spinal cord. Intrathecal capsaicin (1 μg/site also enhanced B1R mRNA in lumbar spinal cord. NAC (1 g/kg/d × 7 days prevented B1R up-regulation, superoxide anion production and NF-kB activation induced by capsaicin (15 mg/kg. Des-Arg9-BK (9.6 nmol/site, i.t. decreased by 25-30% the nociceptive threshold at 1 min post-injection in capsaicin-treated rats (10-50 mg/kg while it was without effect in control rats. Des-Arg9-BK-induced thermal hyperalgesia was blocked by capsazepine, SB-366791 and by antagonists/inhibitors of B1R (SSR240612, 10 mg/kg, p

Kallikrein gene-modified EPCs induce angiogenesis in rats with ischemic hindlimb and correlate with integrin αvβ3 expression.

Directory of Open Access Journals (Sweden)

Shen Shen Fu

Full Text Available BACKGROUND: Human tissue kallikrein (hTK plays an essential role in the physiological and pathological mechanisms of blood vessels. This study aimed to determine whether angiogenesis induced by endothelial progenitor cells (EPCs transduced with the adenovirus-mediated hTK gene could improve blood flow in rat hindlimb ischemia in vivo and to establish a promising mechanism in vitro. METHODS: EPCs transduced with adenovirus encoding hTK-162 (i.e., Ad/hTK-transduced EPCs or Ad/GFP-transduced EPCs were administered to Wister rats with hindlimb ischemia through therapeutic neovascularization. Muscular capillary density (MCD, blood flow (BF, and the number of myofibers were measured at days 7, 14, and 21 after treatment. Expressions of integrin αvβ3 and endothelial nitric oxide synthase (eNOS were detected on the surface of EPCs. RESULTS: MCD, BF, and the number of myofibers in rats with Ad/hTK-transduced EPCs remarkably increased at day 21 after treatment compared with rats with Ad/GFP-transduced EPCs or the control group (P<0.01. Expressions of integrin αvβ3 and eNOS protein on the surface of EPCs also increased in rats with Ad/hTK-transduced EPCs. The levels of integrin αvβ3 expression were reduced by PI3K and eNOS blockade, and the inhibitor of integrin αvβ3 abrogated the migration and adhesion of hTK-transduced EPCs (P<0.05. CONCLUSION: hTK gene delivery in vivo improves the natural angiogenic response to ischemia. The ability of hTK gene-transduced EPCs can be enhanced in vitro, in which integrin αvβ3 plays a role in the process.

Anwendung von kathodischen Korrosionsschutzmaßnahmen bei 30 Spannbetonbrücken in den Niederlanden

NARCIS (Netherlands)

Hondel, H. van den; Klamer, E.L.; Gulikers, J.; Polder, R.B.

2015-01-01

Die oberste niederländische Straßen- und Wasserbaubehörde (Rijkswaterstaat) hat im Hinblick auf die langfristige Instandhaltung ihrer Infrastruktureinrichtungen über 1500 Endverankerungsbereiche von Spannbetonbrückenträgern instandgesetzt und einer kathodischen Korrosionsschutzbehandlung (KKS)

Hormonal derangement and abnormal renal haemodynamics in the ...

African Journals Online (AJOL)

seconds under pentobarbital anaesthesia. A reduction in urinary kallikrein excretion was found (P<0.05) while the renal cortex kallikrein activity remained normal one hour after scalding. An increase in plasma renin activity (P<0.05) and a marked increase in plasma Beta-endorphin concentration (P<0.005) was observed.

Importance of the terminal α-amino group of bradykinin and some kynins on capillary permeability increase

International Nuclear Information System (INIS)

Sugavara, S.

1979-01-01

A simple and reliable method is described for the quantitative evaluation of vascular permeability increase induced by vasoactive drugs with Evans blue labelled with iodine-125 or 131. By using this method the importance of α-amino group of bradykinin (Bk), kallidin (Kd) and methionyl-kallidin (Met-Kd) on the biological activity were studied after reacting the kinins with pyridoxal 5'-phosphate followed by reduction with sodium borohydride. Phosphopyridoxyl-kinins were formed leaving free the guanidino groups. Aminoacid analysis of phosphopyridoxyl-kinin showed that the efficiency of the reaction was extremely good in the blockage of α-amino groups [phosphopyridoxyl-bradikinin (PP-Bk) = 98,8%, phosphopyridoxyl-kallidin (PP-Kd) = 95,2%, phosphopyridoxyl-methionyl-kallidin (PP-Met-Kd) = 98,0%. Log dose-response curves were obtained for Bk, Kd, Met-Kd, acetyl-bradykinin (Ac-Bk), PP-Bk, PP-Kd and PP-Met-Kd and the relative potencies calculated through the Lineweaver-Burk plots. The relative potencies were: PP-Bk about 16% the activity of Bk, Ac-Bk about 31% the activity of Bk, PP-Kd about 17% the activity of Kd, PP-Met-Kd about 12% the activity of Met-Kd. The results show that the terminal α-amino group of kinins is important in the mechanisms of biological activity. (Author) [pt

A Highly Sensitive Porous Silicon (P-Si)-Based Human Kallikrein 2 (hK2) Immunoassay Platform toward Accurate Diagnosis of Prostate Cancer.

Science.gov (United States)

Lee, Sang Wook; Hosokawa, Kazuo; Kim, Soyoun; Jeong, Ok Chan; Lilja, Hans; Laurell, Thomas; Maeda, Mizuo

2015-05-22

Levels of total human kallikrein 2 (hK2), a protein involved the pathology of prostate cancer (PCa), could be used as a biomarker to aid in the diagnosis of this disease. In this study, we report on a porous silicon antibody immunoassay platform for the detection of serum levels of total hK2. The surface of porous silicon has a 3-dimensional macro- and nanoporous structure, which offers a large binding capacity for capturing probe molecules. The tailored pore size of the porous silicon also allows efficient immobilization of antibodies by surface adsorption, and does not require chemical immobilization. Monoclonal hK2 capture antibody (6B7) was dispensed onto P-Si chip using a piezoelectric dispenser. In total 13 × 13 arrays (169 spots) were spotted on the chip with its single spot volume of 300 pL. For an optimization of capture antibody condition, we firstly performed an immunoassay of the P-Si microarray under a titration series of hK2 in pure buffer (PBS) at three different antibody densities (75, 100 and 145 µg/mL). The best performance of the microarray platform was seen at 100 µg/mL of the capture antibody concentration (LOD was 100 fg/mL). The platform then was subsequently evaluated for a titration series of serum-spiked hK2 samples. The developed platform utilizes only 15 µL of serum per test and the total assay time is about 3 h, including immobilization of the capture antibody. The detection limit of the hK2 assay was 100 fg/mL in PBS buffer and 1 pg/mL in serum with a dynamic range of 106 (10(-4) to 10(2) ng/mL).

NCBI nr-aa BLAST: CBRC-PHAM-01-0774 [SEVENS

Lifescience Database Archive (English)

Full Text Available ced As A Secretion Protein In E.Coli pdb|3BSQ|B Chain B, Crystal Structure Of Human Kallikrein 7 Produced As... A Secretion Protein In E.Coli pdb|3BSQ|C Chain C, Crystal Structure Of Human Kallikrein 7 Produced As A Secretion Protein In E.Coli 3BSQ 2e-12 89% ...

Radioassay of granulocyte chemotaxis. Studies of human granulocytes and chemotactic factors. [/sup 51/Cr tracer technique

Energy Technology Data Exchange (ETDEWEB)

Gallin, J I

1974-01-01

The above studies demonstrate that the /sup 51/Cr radiolabel chemotactic assay is a relatively simple and objective means for studying leukocyte chemotaxis in both normal and pathological conditions. Application of this method to studies of normal human chemotaxis revealed a relatively narrow range of normal and little day-to-day variability. Analysis of this variability revealed that there is more variability among the response of different granulocytes to a constant chemotactic stimulus than among the chemotactic activity of different sera to a single cell source. Utilizing the /sup 51/Cr radioassay, the abnormal granulocyte chemotactic behavior reported in Chediak-Higashi syndrome and a patient with recurrent pyogenic infections and mucocutaneous candidiasis has been confirmed. The /sup 51/Cr chemotactic assay has also been used to assess the generation of chemotactic activity from human serum and plasma. The in vitro generation of two distinct chemotactic factors were examined; the complement product (C5a) and kallikrein, an enzyme of the kinin-generating pathway. Kinetic analysis of complement-related chemotactic factor formation, utilizing immune complexes or endotoxin to activate normal sera in the presence or absence of EGTA as well as kinetic analysis of activation of C2-deficient human serum, provided an easy means of distinguishing the classical (antibody-mediated) complement pathway from the alternate pathway. Such kinetic analysis is necessary to detect clinically important abnormalities since, after 60 min of generation time, normal chemotactic activity may be present despite complete absence or inhibition of one complement pathway. The chemotactic factor generated by either pathway of complement activation appears to be predominately attributable to C5a.

Snake venom serine proteinases specificity mapping by proteomic identification of cleavage sites.

Science.gov (United States)

Zelanis, André; Huesgen, Pitter F; Oliveira, Ana Karina; Tashima, Alexandre K; Serrano, Solange M T; Overall, Christopher M

2015-01-15

Many snake venom toxins are serine proteases but their specific in vivo targets are mostly unknown. Various act on components of the coagulation cascade, and fibrinolytic and kallikrein-kinin systems to trigger various pathological effects observed in the envenomation. Despite showing high similarity in terms of primary structure snake venom serine proteinases (SVSPs) show exquisite specificity towards macromolecular substrates. Therefore, the characterization of their peptide bond specificity is important for understanding the active site preference associated with effective proteolysis as well as for the design of peptide substrates and inhibitors. Bothrops jararaca contains various SVSPs among which Bothrops protease A is a specific fibrinogenolytic agent and PA-BJ is a platelet-activating enzyme. In this study we used proteome derived peptide libraries in the Proteomic Identification of protease Cleavage Sites (PICS) approach to explore the peptide bond specificity of Bothrops protease A and PA-BJ in order to determine their individual peptide cleavage sequences. A total of 371 cleavage sites (208 for Bothrops protease A and 163 for PA-BJ) were detected and both proteinases displayed a clear preference for arginine at the P1 position. Moreover, the analysis of the specificity profiles of Bothrops protease A and PA-BJ revealed subtle differences in the preferences along P6-P6', despite a common yet unusual preference for Pro at P2. Taken together, these results map the subsite specificity of both SVSPs and shed light in the functional differences between these proteinases. Proteolysis is key to various pathological effects observed upon envenomation by viperid snakes. The use of the Proteomic Identification of protease Cleavage Sites (PICS) approach for the easy mapping of proteinase subsite preferences at both the prime- and non-prime sides concurrently gives rise to a fresh understanding of the interaction of the snake venom serine proteinases with peptide and

Pramana – Journal of Physics | Indian Academy of Sciences

Indian Academy of Sciences (India)

The effect of normal scattering processes is considered to redistribute the phonon momentum in (a) the same phonon branch – KK-S model and (b) between different phonon branches – KK-H model. Simplified thermal conductivity relations are used to estimate the thermal conductivity of germanium, silicon and diamond ...

Effect of normal processes on thermal conductivity of germanium ...

Indian Academy of Sciences (India)

Abstract. The effect of normal scattering processes is considered to redistribute the phonon momentum in (a) the same phonon branch – KK-S model and (b) between differ- ent phonon branches – KK-H model. Simplified thermal conductivity relations are used to estimate the thermal conductivity of germanium, silicon and ...

Biomarkers for Early Detection of Clinically Relevant Prostate Cancer. A Multi-Institutional Validation Trial

Science.gov (United States)

2016-10-01

aim 2: Evaluate a panel of four-kallikrein plasma-based markers to determine the presence of or progression to clinically relevant prostate cancer...and sent to Genomic Health, Inc. for processing. Task 3: Analysis of scientific Aim 2: Evaluate a panel of four-kallikrein plasma-based markers to...site: FHCRC) PCA3 and the TMPRSS2:ERG fusion are prostate cancer-specific biomarkers that hold promise for stratifying risk in the setting of AS

A Systematic Review and Meta-analysis of the Diagnostic Accuracy of Prostate Health Index and 4-Kallikrein Panel Score in Predicting Overall and High-grade Prostate Cancer.

Science.gov (United States)

Russo, Giorgio Ivan; Regis, Federica; Castelli, Tommaso; Favilla, Vincenzo; Privitera, Salvatore; Giardina, Raimondo; Cimino, Sebastiano; Morgia, Giuseppe

2017-08-01

Markers for prostate cancer (PCa) have progressed over recent years. In particular, the prostate health index (PHI) and the 4-kallikrein (4K) panel have been demonstrated to improve the diagnosis of PCa. We aimed to review the diagnostic accuracy of PHI and the 4K panel for PCa detection. We performed a systematic literature search of PubMed, EMBASE, Cochrane, and Academic One File databases until July 2016. We included diagnostic accuracy studies that used PHI or 4K panel for the diagnosis of PCa or high-grade PCa. The methodological quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Twenty-eight studies including 16,762 patients have been included for the analysis. The pooled data showed a sensitivity of 0.89 and 0.74 for PHI and 4K panel, respectively, for PCa detection and a pooled specificity of 0.34 and 0.60 for PHI and 4K panel, respectively. The derived area under the curve (AUC) from the hierarchical summary receiver operating characteristic (HSROC) showed an accuracy of 0.76 and 0.72 for PHI and 4K panel respectively. For high-grade PCa detection, the pooled sensitivity was 0.93 and 0.87 for PHI and 4K panel, respectively, whereas the pooled specificity was 0.34 and 0.61 for PHI and 4K panel, respectively. The derived AUC from the HSROC showed an accuracy of 0.82 and 0.81 for PHI and 4K panel, respectively. Both PHI and the 4K panel provided good diagnostic accuracy in detecting overall and high-grade PCa. Copyright © 2016 Elsevier Inc. All rights reserved.

Prostate-specific antigen (PSA/hK3): a further player in the field of breast cancer diagnostics?

OpenAIRE

Mannello, Ferdinando; Gazzanelli, Giancarlo

2001-01-01

Since its identification, much information has been obtained about prostate-specific antigen (PSA, or human glandular kallikrein 3 [hK3]), a kallikrein-like serine protease that is the most valuable tumour marker for the screening, diagnosis and management of human prostate carcinoma. Recently, it has become widely accepted that PSA is also present in many nonprostatic sources, casting doubts about the specificity of its tissue expression. Here we summarize the findings on the biomolecular ex...

Waste management concept during dismantling of KKS NPP in Germany

International Nuclear Information System (INIS)

Bacmeister, Georg U.

2008-01-01

Full text: This paper gives an overview on the waste management of NPP Stade during dismantling. The general idea is to reduce the radioactive waste to about three percentage of the complete dismantling mass. The NPP Stade in Germany was shut down in November 2003. After a transient phase the license for dismantling was given in 2005. In the following 8 years about 20.000 tones of steel and 120.000 tones of concrete will be put out by the dismantling. The yearly output of steel will by about 100 times higher than during the running time of the NNP. For this a new processes for waste management had to be installed. The waste management during dismantling focus on free release (about 97%). Beside some minor exception, the rest is deemed to be radioactive waste. This will be collected in 1000 packages, which are ready to be sent to a final storage. As until now in Germany no final storage is open (and sending of radioactive waste to another country is forbidden), the NNP Stade build an intermediate storage, where the packages may by saved for longest 40 years. The clearance procedure in Germany is regulated in the radiation protection ordinances. It is based on a nuclide specific set of clearance levels. To fulfil these demands the NNP Stade chose a semi automated system for characterization and documentation, which we develop in accordance to our release license. It guaranties a most accurate determination of the relevant nuclides for a set of dismantling material (some 10 to 100 tones). After the characterization only the gamma-activity of the material is measured in boxes of about 500 kg. A short comparison of the chosen procedure with other options, possible in Germany will be given and the decision from the collaboration with the NPP in Barsebaeck, Sweden, will be withdrawn. Beside the free release different options are used for waste management, like incineration, sending to landfill or reuse in nuclear industry. The waste management of the NNP Stade take

[Angiotensin converting enzyme: the antigenic properties of the domain, role in Alzheimer's disease and tumor progression].

Science.gov (United States)

Kugaevskaya, E V; Timoshenko, O S; Solovyeva, N I

2015-01-01

Angiotensin converting enzyme (ACE, EC 3.4.15.1) was discovered and characterized in the Laboratory of biochemistry and chemical pathology of proteins under the direction of academician V.N. Orekhovich, where its physiological function, associated with a key role in the regulation of the renin-angiotensin (RAS) and the kallikrein-kinin systems that control blood flow in the body and homeostasis was first deciphered. We carried out a search for structural differences between the two highly homologous domains (N- and C-domains) of somatic ACE (sACE); it was based on a comparative analysis of antigenic determinants (or B-epitopes) of both domains. The revealed epitopes were classified with variable and conserved regions and functionally important sites of the molecule ACE. Essential difference was demonstrated between locations of the epitopes in the N- and C-domains. These data indicate the existence of structural differences between the domains of sACE. We studied the role of the domains of ACE in the metabolism of human amyloid beta peptide (Ab) - the main component of senile plaques, found in the brains of patients with Alzheimer's disease (AD). Our results demonstrated that only N-domain ACE cleaved the Ab between residues R5-H6, while, the C-domain of ACE failed to hydrolyze this region. In addition, the effect of post-translational modifications of Ab on its hydrolysis by the ACE was investigated. We show that isomerization of residue D7, a common non-enzymatic age-related modification found in AD-associated species, does not reduce the affinity of the peptide to the N-domain of ACE, and conversely, it increases. According to our data, the role of ACE in the metabolism of Ab becomes more significant in the development of AD. RAS is involved in malignant transformation and tumor progression. RAS components, including ACE and angiotensin II receptors type 1 (AT1R) are expressed in various human tumors. We found a significant increase in the level of ACE activity

Status and perspectives of the dismantling of nuclear power plants in Germany (Dismantling monitoring 2015); Stand und Perspektiven des Rueckbaus von Kernkraftwerken in Deutschland (''Rueckbau-Monitoring 2015'')

Energy Technology Data Exchange (ETDEWEB)

Wealer, Ben; Seidel, Jan Paul [Technische Univ. Berlin (Germany); Gerbaulet, Clemens; Hirschhausen, Christian von [Technische Univ. Berlin (Germany); Deutsches Institut fuer Wirtschaftsforschung, Berlin (Germany)

2015-11-15

The dismantling monitoring 2015 covers the nuclear power plants HDR Grosswelzheim, Niederaichbach (KKN), MZFR Karlsruhe, Lingen (KWL), Gundremmingen unit A (KRB-A), VAK Kahl, Muehlheim-Kaerlich (KMK), THTR-300 Hamm-Uentrop, AVR Juelich, Greifswald (KGR 1-5), KNK II Karlsruhe, Rheinsberg (KKR), Wuergassen (KWW), Stade (KKS), Obrigheim (KWO), SNR 300. The post-operational phase activities of other shut-down nuclear power plants and the active companies are summarized.

Synthesis of the proteinase inhibitor LEKTI domain 6 by the fragment condensation method and regioselective disulfide bond formation.

Science.gov (United States)

Vasileiou, Zoe; Barlos, Kostas K; Gatos, Dimitrios; Adermann, Knut; Deraison, Celine; Barlos, Kleomenis

2010-01-01

Proteinase inhibitors are of high pharmaceutical interest and are drug candidates for a variety of indications. Specific kallikrein inhibitors are important for their antitumor activity and their potential application to the treatment of skin diseases. In this study we describe the synthesis of domain 6 of the kallikrein inhibitor Lympho-Epithilial Kazal-Type Inhibitor (LEKTI) by the fragment condensation method and site-directed cystine bridge formation. To obtain the linear LEKTI precursor, the condensation was best performed in solution, coupling the protected fragment 1-22 to 23-68. This method yielded LEKTI domain 6 of high purity and equipotent to the recombinantly produced peptide. (c) 2010 Wiley Periodicals, Inc.

Stade nuclear power station (KKS): four giants on tour

International Nuclear Information System (INIS)

Beverungen, M.; Viermann, J.

2008-01-01

The Stade nuclear power station was the first nuclear power plant in the Federal Republic of Germany to deliver heat in addition to electricity. Since 1984, district heat was distributed to a saltworks nearby. The power plant, which is situated on the banks of the river Elbe, was commissioned in 1972 after approximately 4 years of construction. Together with the Wuergassen plant, it was among the first commercial nuclear power plants in this country. E.ON Kernkraft holds a 2/3 interest, Vattenfall Europe a 1/3 interest in the nuclear power plant. The Stade nuclear power station was decommissioned on November 14, 2003 for economic reasons which, in part, were also politically motivated. In September 2005, the permit for demolition of the nuclear part was granted. The release from supervision under the Atomic Energy Act is expected for 2014. In the course of demolition, the 4 steam generators of the Stade nuclear power station were removed. These components, which have an aggregate weight of approx. 660 tons, are to be safely re-used in Sweden. In September 2007, the steam generators were loaded on board the Swedish special vessel, MS Sigyn, by means of a floating crane. After shipment to Sweden, heavy-duty trucks carried the components to the processing hall of Studsvik AB for further treatment. After 6 months of treatment, the contaminated inner surfaces of the tube bundles of the steam generators have been decontaminated successfully, among other items. This has increased the volume of material available for recycling and thus decreased the volume of residues. (orig.)

Comparative studies on the anti-inflammatory and analgesic activity ...

African Journals Online (AJOL)

USER

2010-05-17

May 17, 2010 ... breast cancer and other inflammatory-related ailments in South Africa. The aqueous ... such as stomach, bladder, colon, liver and bile duct have ..... kinin receptors in formalin-induced nociceptive response in mouse. Brit.

Identification of three novel peptides isolated from the venom of the neotropical social wasp Polistes major major

Czech Academy of Sciences Publication Activity Database

Čeřovský, Václav; Pohl, J.; Yang, Z.; Alam, N.; Attygalle, A. B.

2007-01-01

Roč. 13, č. 7 (2007), s. 445-450 ISSN 1075-2617 Institutional research plan: CEZ:AV0Z40550506 Keywords : mastoparans * wasp kinins * chemotactic peptides Subject RIV: CC - Organic Chemistry Impact factor: 1.768, year: 2007

Kinetics of Iodine 131 labelled fibrinogen in cancerous patients. Pharmacological study

International Nuclear Information System (INIS)

Boneu-Valmalette, Andree; Bugat, Roland; David, J.-F.; Combes, P.-F.

1977-01-01

The results obtained in a previous study using 131 I fibrinogen in cancerous patients suggested a local intravascular clotting process. In order to elucidate the mechanism of fibrinogen kinetic abnormalities different drugs including heparin, prednisone, ticlopidin, aspirin and indomethacin were administred in 68 patients and their effects evaluated by change in the 131 I fibrinogen disappearance rate. The results suggest that these drugs may counteract with the early stages of coagulation (kinin-forming system, factor XII) and that abnormal 131 I fibrinogen kinetic in cancer would be a non specific phenomenon [fr

Türkiye’de Vergi Gelirleri ile Ekonomik Kalkınma Arasındaki İlişki: Frekans Alanı Nedensellik Analizi

Directory of Open Access Journals (Sweden)

Mehmet Vahit EREN

2018-01-01

Full Text Available Çalışmanın amacı, Türkiye’de 1975-2013 dönemine ait yıllık verilerle vergi gelirleri ile kalkınma arasındaki ilişkinin varlığını araştırmakla beraber söz konusu ilişkinin yönünü farklı ekonometrik testlerle analiz etmektir. Hacker ve Hatemi nedensellik testi bulgularına göre, dolaylı vergi gelirlerinden kalkınmaya doğru tek yönlü; Breitung ve Caldelon frekans alanı nedensellik testi ise toplam vergi gelirlerinden kalkınmaya, dolaysız vergi gelirlerinden kalkınmaya ve kalkınmadan dolaylı vergi gelirlerine doğru tek yönlü ilişkiler tespit edilmiştir.

Stade. Decommissioning and dismantling of the nuclear power plant - from the nuclear power plant to the green lawn. 3. ed.

International Nuclear Information System (INIS)

2008-01-01

The nuclear power plant Stade (KKS) was shutdown in 2003 and is being dismantled since 2005. The contribution covers the following issues: What means decommissioning and dismantling? What was the reason for decommissioning? What experiences on the dismantling of nuclear power plants are available? What is the dismantling procedure? What challenges for the power plant personal result from dismantling? What happens with the deconstruction material? What happens with the resulting free area (the ''green lawn'')? What is the legal frame work for dismantling?

A leucokinin mimic elicits aversive behavior in mosquito Aedes aegypti (L.) and inhibits the sugar taste neuron

Science.gov (United States)

Insect kinins (leucokinins) are multifunctional peptides acting as neurohormones and neurotransmitters. In females of the mosquito vector Aedes aegypti (L.), aedeskinins are known to stimulate fluid secretion from the renal organs (Malpighian tubules) and hindgut contractions by activating a G prot...

The Urine Proteome as a Biomarker of Radiation Injury

Science.gov (United States)

Sharma, Mukut; Halligan, Brian D.; Wakim, Bassam T.; Savin, Virginia J.; Cohen, Eric P.; Moulder, John E.

2009-01-01

Terrorist attacks or nuclear accidents could expose large numbers of people to ionizing radiation, and early biomarkers of radiation injury would be critical for triage, treatment and follow-up of such individuals. However, no such biomarkers have yet been proven to exist. We tested the potential of high throughput proteomics to identify protein biomarkers of radiation injury after total body X-ray irradiation in a rat model. Subtle functional changes in the kidney are suggested by an increased glomerular permeability for macromolecules measured within 24 hours after TBI. Ultrastructural changes in glomerular podocytes include partial loss of the interdigitating organization of foot processes. Analysis of urine by LC-MS/MS and 2D-GE showed significant changes in the urine proteome within 24 hours after TBI. Tissue kallikrein 1-related peptidase, cysteine proteinase inhibitor cystatin C and oxidized histidine were found to be increased while a number of proteinase inhibitors including kallikrein-binding protein and albumin were found to be decreased post-irradiation. Thus, TBI causes immediately detectable changes in renal structure and function and in the urinary protein profile. This suggests that both systemic and renal changes are induced by radiation and it may be possible to identify a set of biomarkers unique to radiation injury. PMID:19746194

The Urine Proteome as a Biomarker of Radiation Injury: Submitted to Proteomics- Clinical Applications Special Issue: "Renal and Urinary Proteomics (Thongboonkerd)"

Science.gov (United States)

Sharma, Mukut; Halligan, Brian D; Wakim, Bassam T; Savin, Virginia J; Cohen, Eric P; Moulder, John E

2008-06-18

Terrorist attacks or nuclear accidents could expose large numbers of people to ionizing radiation, and early biomarkers of radiation injury would be critical for triage, treatment and follow-up of such individuals. However, no such biomarkers have yet been proven to exist. We tested the potential of high throughput proteomics to identify protein biomarkers of radiation injury after total body X-ray irradiation in a rat model. Subtle functional changes in the kidney are suggested by an increased glomerular permeability for macromolecules measured within 24 hours after TBI. Ultrastructural changes in glomerular podocytes include partial loss of the interdigitating organization of foot processes. Analysis of urine by LC-MS/MS and 2D-GE showed significant changes in the urine proteome within 24 hours after TBI. Tissue kallikrein 1-related peptidase, cysteine proteinase inhibitor cystatin C and oxidized histidine were found to be increased while a number of proteinase inhibitors including kallikrein-binding protein and albumin were found to be decreased post-irradiation. Thus, TBI causes immediately detectable changes in renal structure and function and in the urinary protein profile. This suggests that both systemic and renal changes are induced by radiation and it may be possible to identify a set of biomarkers unique to radiation injury.

Hereditary angioedema

Science.gov (United States)

... disease; HAE- Hereditary angioedema; Kallikrein inhibitor-HAE: bradykinin receptor antagonist-HAE; C1-inhibitors-HAE; Hives-HAE ... aunt, uncle, or grandparent. Dental procedures, sickness (including colds and the flu), and surgery may trigger HAE ...

Cyclooxygenase-2 and hypoxia-regulated proteins are modulated by basic fibroblast growth factor in acute renal failure

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Sandra Villanueva

2012-01-01

Full Text Available Acute renal failure (ARF can be caused by injuries that induce tissue hypoxia, which in turn can trigger adaptive or inflammatory responses. We previously showed the participation of basic fibroblast growth factor (FGF-2 in renal repair. Based on this, the aim of this study was to analyze the effect of FGF-2 signaling pathway manipulation at hypoxia-induced protein levels, as well as in key proteins from the vasoactive systems of the kidney. We injected rat kidneys with FGF-2 recombinant protein (r-FGF or FGF-2 receptor antisense oligonucleotide (FGFR2-ASO after bilateral ischemia, and evaluated the presence of iNOS, EPO and HO-1, in representation of hypoxia-induced proteins, as well as COX-2, renin, kallikrein, and B2KR, in representation of the vasoactive systems of the kidney. A reduction in iNOS, HO-1, EPO, renin, kallikrein, B2KR, and in renal damage was observed in animals treated with r-FGF. The opposite effect was found with FGF-2 receptor down-regulation. In contrast, COX-2 protein levels were higher in kidneys treated with r-FGF and lower in those that received FGFR2-ASO, as compared to saline treated kidneys. These results suggest that the protective role of FGF-2 in the pathogenesis of ARF induced by I/R is a complex process, through which a differential regulation of metabolic pathways takes place.

Deciphering defective amelogenesis using in vitro culture systems.

Science.gov (United States)

Arinawati, Dian Yosi; Miyoshi, Keiko; Tanimura, Ayako; Horiguchi, Taigo; Hagita, Hiroko; Noma, Takafumi

2018-04-01

The conventional two-dimensional (2D) in vitro culture system is frequently used to analyze the gene expression with or without extracellular signals. However, the cells derived from primary culture and cell lines frequently deviate the gene expression profile compared to the corresponding in vivo samples, which sometimes misleads the actual gene regulation in vivo. To overcome this gap, we developed the comparative 2D and 3D in vitro culture systems and applied them to the genetic study of amelogenesis imperfecta (AI) as a model. Recently, we found specificity protein 6 (Sp6) mutation in an autosomal-recessive AI rat that was previously named AMI. We constructed 3D structure of ARE-B30 cells (AMI-derived rat dental epithelial cells) or G5 (control wild type cells) combined with RPC-C2A cells (rat pulp cell line) separated by the collagen membrane, while in 2D structure, ARE-B30 or G5 was cultured with or without the collagen membrane. Comparative analysis of amelogenesis-related gene expression in ARE-B30 and G5 using our 2D and 3D in vitro systems revealed distinct expression profiles, showing the causative outcomes. Bone morphogenetic protein 2 and follistatin were reciprocally expressed in G5, but not in ARE-B30 cells. All-or-none expression of amelotin, kallikrein-related peptidase 4, and nerve growth factor receptor was observed in both cell types. In conclusion, our in vitro culture systems detected the phenotypical differences in the expression of the stage-specific amelogenesis-related genes. Parallel analysis with 2D and 3D culture systems may provide a platform to understand the molecular basis for defective amelogenesis caused by Sp6 mutation. Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

[Levels of emotional intelligence and types of attachment among third year students of the Faculty of Health Science and the Faculty of Medicine--a comparative analysis].

Science.gov (United States)

Tyszkiewicz-Bandur, Monika

2013-01-01

For the purposes of this research attachment theory was incorporated into the concept of emotional intelligence. The methodological starting point of this study was the assumption that the level of emotional intelligence and social competence is related to a steady feature, namely the type of attachment. Standardized questionnaires available in the Laboratory of Psychological Tests of the Polish Psychological Association were chosen to measure the level of emotional intelligence. However, the type of attachment was studied by Bartholomew's Self Description Test in my own translation. The study involved two groups of students, who were compared: 147 people from the Faculty of Health Sciences/Faculty of Nursing (nursing, midwifery, health promotion, cosmetology, emergency medicine, dietetics), and 181 people from the Faculty of Medicine (medicine), students in their second and third years of studies. A total of 328 people, aged 19-24, were tested. On the basis of the results it was stated that students of the Faculty of Health Sciences/Faculty of Nursing, as compared to students of the Faculty of Medicine, received significantly higher scores on the scale of the social competence scale, which investigated the efficiency of their behaviour in intimate situations. Moreover, statistical analysis proved that students of the Faculty of Health Sciences showed significantly higher scores than those studying at the Faculty of Medicine in the following fields: KKS-I subscale assessing social competencies in--conditioning effective behaviour in intimate situations, emotional intelligence measured with the INTE questionnaire,--awareness of their own emotional states and understanding their causes (DINEMO-I),--ability to recognize emotions in other people and understanding the reasons for the reactions expressed by them (DINEMO-Others)--emotional intelligence measured with the DINEMO questionnaire (DINEMO-general score). Women from both faculties showed higher social competence

The added value of percentage of free to total prostate-specific antigen, PCA3, and a kallikrein panel to the ERSPC risk calculator for prostate cancer in prescreened men.

Science.gov (United States)

Vedder, Moniek M; de Bekker-Grob, Esther W; Lilja, Hans G; Vickers, Andrew J; van Leenders, Geert J L H; Steyerberg, Ewout W; Roobol, Monique J

2014-12-01

Prostate-specific antigen (PSA) testing has limited accuracy for the early detection of prostate cancer (PCa). To assess the value added by percentage of free to total PSA (%fPSA), prostate cancer antigen 3 (PCA3), and a kallikrein panel (4k-panel) to the European Randomised Study of Screening for Prostate Cancer (ERSPC) multivariable prediction models: risk calculator (RC) 4, including transrectal ultrasound, and RC 4 plus digital rectal examination (4+DRE) for prescreened men. Participants were invited for rescreening between October 2007 and February 2009 within the Dutch part of the ERSPC study. Biopsies were taken in men with a PSA level ≥3.0 ng/ml or a PCA3 score ≥10. Additional analyses of the 4k-panel were done on serum samples. Outcome was defined as PCa detectable by sextant biopsy. Receiver operating characteristic curve and decision curve analyses were performed to compare the predictive capabilities of %fPSA, PCA3, 4k-panel, the ERSPC RCs, and their combinations in logistic regression models. PCa was detected in 119 of 708 men. The %fPSA did not perform better univariately or added to the RCs compared with the RCs alone. In 202 men with an elevated PSA, the 4k-panel discriminated better than PCA3 when modelled univariately (area under the curve [AUC]: 0.78 vs. 0.62; p=0.01). The multivariable models with PCA3 or the 4k-panel were equivalent (AUC: 0.80 for RC 4+DRE). In the total population, PCA3 discriminated better than the 4k-panel (univariate AUC: 0.63 vs. 0.56; p=0.05). There was no statistically significant difference between the multivariable model with PCA3 (AUC: 0.73) versus the model with the 4k-panel (AUC: 0.71; p=0.18). The multivariable model with PCA3 performed better than the reference model (0.73 vs. 0.70; p=0.02). Decision curves confirmed these patterns, although numbers were small. Both PCA3 and, to a lesser extent, a 4k-panel have added value to the DRE-based ERSPC RC in detecting PCa in prescreened men. We studied the added

Expression and localization of tissue factor pathway inhibitor-2 in normal and atherosclerotic human vessels

NARCIS (Netherlands)

Crawley, James T. B.; Goulding, David A.; Ferreira, Valérie; Severs, Nicholas J.; Lupu, Florea

2002-01-01

Tissue factor pathway inhibitor-2 (TFPI-2) is a Kunitz-type, serine protease inhibitor with inhibitory activity toward activated factor XI, plasma kallikrein, plasmin, certain matrix metalloproteinases, and the tissue factor:activated factor VII complex. In this study, we investigated TFPI-2

Bradykinin Contributes to Sympathetic and Pressor Responses Evoked by Activation of Skeletal Muscle Afferents P2X in Heart Failure

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Jihong Xing

2016-11-01

Full Text Available Background/Aims: Published data suggest that purinergic P2X receptors of muscle afferent nerves contribute to the enhanced sympathetic nervous activity (SNA and blood pressure (BP responses during static exercise in heart failure (HF. In this study, we examined engagement of bradykinin (BK in regulating responses of SNA and BP evoked by P2X stimulation in rats with HF. We further examined cellular mechanisms responsible for BK. We hypothesized that BK potentiates P2X currents of muscle dorsal root ganglion (DRG neurons, and this effect is greater in HF due to upregulation of BK kinin B2 and P2X3 receptor. As a result, BK amplifies muscle afferents P2X-mediated SNA and BP responses. Methods: Renal SNA and BP responses were recorded in control rats and rats with HF. Western Blot analysis and patch-clamp methods were employed to examine the receptor expression and function of DRG neurons involved in the effects of BK. Results: BK injected into the arterial blood supply of the hindlimb muscles heightened the reflex SNA and BP responses induced by P2X activation with α,β-methylene ATP to a greater degree in HF rats. In addition, HF upregulated the protein expression of kinin B2 and P2X3 in DRG and the prior application of BK increased the magnitude of α,β-methylene ATP-induced currents in muscle DRG neurons from HF rats. Conclusion: BK plays a facilitating role in modulating muscle afferent P2X-engaged reflex sympathetic and pressor responses. In HF, P2X responsivness is augmented due to increases in expression of kinin B2 and P2X3 receptors and P2X current activity.

B1 but not B2 bradykinin receptor agonists promote DU145 prostate ...

African Journals Online (AJOL)

University of KwaZulu-Natal,. Private Bag X7, Congella 4013, Durban,. South Africa. Tel: +27 31 2604486. Fax: +27 31 2604338. Email: naidoot@ukzn.ac.za ..... ME, Leeb-Lundberg LM,Daaka Y. Requirement for di- rect cross-talk between b1 and b2 kinin receptors for the proliferation of androgen-insensitive prostate can-.

Defects in Stratum Corneum Desquamation Are the Predominant Effect of Impaired ABCA12 Function in a Novel Mouse Model of Harlequin Ichthyosis.

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Lei Zhang

Full Text Available Harlequin Ichthyosis is a severe skin disease caused by mutations in the human gene encoding ABCA12. Here, we characterize a novel mutation in intron 29 of the mouse Abca12 gene that leads to the loss of a 5' splice donor site and truncation of the Abca12 RNA transcript. Homozygous mutants of this smooth skin or smsk allele die perinatally with shiny translucent skin, typical of animal models of Harlequin Ichthyosis. Characterization of smsk mutant skin showed that the delivery of glucosylceramides and CORNEODESMOSIN was defective, while ultrastructural analysis revealed abnormal lamellar bodies and the absence of lipid lamellae in smsk epidermis. Unexpectedly, mutant stratum corneum remained intact when subjected to harsh chemical dissociation procedures. Moreover, both KALLIKREIN 5 and -7 were drastically decreased, with retention of desmoplakin in mutant SC. In cultured wild type keratinocytes, both KALLIKREIN 5 and -7 colocalized with ceramide metabolites following calcium-induced differentiation. Reducing the intracellular levels of glucosylceramide with a glucosylceramide synthase inhibitor resulted in decreased secretion of KALLIKREIN proteases by wild type keratinocytes, but not by smsk mutant keratinocytes. Together, these findings suggest an essential role for ABCA12 in transferring not only lipids, which are required for the formation of multilamellar structures in the stratum corneum, but also proteolytic enzymes that are required for normal desquamation. Smsk mutant mice recapitulate many of the pathological features of HI and can be used to explore novel topical therapies against a potentially lethal and debilitating neonatal disease.

Human seminal proteinase and prostate-specific antigen are the ...

Indian Academy of Sciences (India)

https://www.ias.ac.in/article/fulltext/jbsc/033/02/0195-0207. Keywords. Kallikrein; prostate cancer biomarker; proteinase activity; seminal plasma; tumour proliferation and metastasis; therapeutic target. Abstract. Human seminal proteinase and prostate-specific antigen (PSA) were each isolated from human seminal fluid and ...

Methylation of Promoter Regions of Genes of the Human Intrauterine Renin Angiotensin System and Their Expression

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Shane D. Sykes

2015-01-01

Full Text Available The intrauterine renin angiotensin system (RAS is implicated in placentation and labour onset. Here we investigate whether promoter methylation of RAS genes changes with gestation or labour and if it affects gene expression. Early gestation amnion and placenta were studied, as were term amnion, decidua, and placenta collected before labour (at elective caesarean section or after spontaneous labour and delivery. The expression and degree of methylation of the prorenin receptor (ATP6AP2, angiotensin converting enzyme (ACE, angiotensin II type 1 receptor (AGTR1, and two proteases that can activate prorenin (kallikrein, KLK1, and cathepsin D, CTSD were measured by qPCR and a DNA methylation array. There was no effect of gestation or labour on the methylation of RAS genes and CTSD. Amnion and decidua displayed strong correlations between the percent hypermethylation of RAS genes and CTSD, suggestive of global methylation. There were no correlations between the degree of methylation and mRNA abundance of any genes studied. KLK1 was the most methylated gene and the proportion of hypermethylated KLK1 alleles was lower in placenta than decidua. The presence of intermediate methylated alleles of KLK1 in early gestation placenta and in amnion after labour suggests that KLK1 methylation is uniquely dynamic in these tissues.

Molecular Structures and Dynamics of the Stepwise Activation Mechanism of a Matrix Metalloproteinase Zymogen: Challenging the Cysteine Switch Dogma

International Nuclear Information System (INIS)

Rosenblum, G.; Meroueh, S.; Toth, M.; Fisher, J.; Fridman, R.; Mobashery, S.; Sagi, I.

2007-01-01

Activation of matrix metalloproteinase zymogen (pro-MMP) is a vital homeostatic process, yet its molecular basis remains unresolved. Using stopped-flow X-ray spectroscopy of the active site zinc ion, we determined the temporal sequence of pro-MMP-9 activation catalyzed by tissue kallikrein protease in milliseconds to several minutes. The identity of three intermediates seen by X-ray spectroscopy was corroborated by molecular dynamics simulations and quantum mechanics/molecular mechanics calculations. The cysteine-zinc interaction that maintains enzyme latency is disrupted via active-site proton transfers that mediate transient metal-protein coordination events and eventual binding of water. Unexpectedly, these events ensue as a direct result of complexation of pro-MMP-9 and kallikrein and occur before proteolysis and eventual dissociation of the pro-peptide from the catalytic site. Here we demonstrate the synergism among long-range protein conformational transitions, local structural rearrangements, and fine atomic events in the process of zymogen activation.

Functions of KLK4 and MMP-20 in dental enamel formation

Science.gov (United States)

Lu, Yuhe; Papagerakis, Petros; Yamakoshi, Yasuo; Hu, Jan C-C.; Bartlett, John D.; Simmer, James P.

2009-01-01

Two proteases are secreted into the enamel matrix of developing teeth. The early protease is enamelysin (MMP-20). The late protease is kallikrein 4 (KLK4). Mutations in MMP20 and KLK4 both cause autosomal recessive amelogenesis imperfecta, a condition featuring soft, porous enamel containing residual protein. MMP-20 is secreted along with enamel proteins by secretory stage ameloblasts. Enamel protein cleavage products accumulate in the space between the crystal ribbons, helping to support them. MMP-20 steadily cleaves accumulated enamel proteins, so their concentration decreases with depth. Kallikrein 4 is secreted by transition and maturation stage ameloblasts. KLK4 aggressively degrades the retained organic matrix following the termination of enamel protein secretion. The principle functions of MMP-20 and KLK4 in dental enamel formation are to facilitate the orderly replacement of organic matrix with mineral, generating an enamel layer that is harder, less porous, and unstained by retained enamel proteins. PMID:18627287

Emerging biomarkers in the diagnosis of prostate cancer

Directory of Open Access Journals (Sweden)

Filella X

2018-05-01

Full Text Available Xavier Filella, Esther Fernández-Galan, Rosa Fernández Bonifacio, Laura Foj Department of Biochemistry and Molecular Genetics (CDB, Hospital Clínic, IDIBAPS, Barcelona, Catalonia, Spain Abstract: Prostate cancer (PCa is the second most common cancer in men worldwide. A large proportion of PCa are latent, never destined to progress or affect the patients’ life. It is of utmost importance to identify which PCa are destined to progress and which would benefit from an early radical treatment. Prostate-specific antigen (PSA remains the most used test to detect PCa. Its limited specificity and an elevated rate of overdiagnosis are the main problems associated with PSA testing. New PCa biomarkers have been proposed to improve the accuracy of PSA in the management of early PCa. Commercially available biomarkers such as PCA3 score, Prostate Health Index (PHI, and the four-kallikrein panel are used with the purpose of reducing the number of unnecessary biopsies and providing information related to the aggressiveness of the tumor. The relationship with PCa aggressiveness seems to be confirmed by PHI and the four-kallikrein panel, but not by the PCA3 score. In this review, we also summarize new promising biomarkers, such as PSA glycoforms, TMPRSS2:ERG fusion gene, microRNAs, circulating tumor cells, androgen receptor variants, and PTEN gene. All these emerging biomarkers could change the management of early PCa, offering more accurate results than PSA. Nonetheless, large prospective studies comparing these new biomarkers among them are required to know their real value in PCa detection and prognosis. Keywords: prostate cancer, PSA, PHI, four-kallikrein panel, PCA3, miRNAs

Recent Advances in Drug-Induced Angioedema

Directory of Open Access Journals (Sweden)

Naoko Inomata

2012-01-01

Full Text Available Angioedema is the end result of deep dermal, subcutaneous and/or mucosal swelling, and is potentially a life- threatening condition in cases where the pharynx or larynx is involved. Drug-induced angioedema has been reported to occur in response to a wide range of drugs and vaccines. Drug-induced angioedema, like other cutaneous drug reactions, has been reported to be most frequently elicited by beta-lactam antibiotics and nonsteroidal anti-inflammatory drugs, although reliable data from epidemiologic studies are scarce. Recent reports suggested an increasing role of angiotensin-converting enzyme inhibitors (ACEIs in the causation of life- threatening angioedema. ACEI-related angioedema is never accompanied by urticaria and occurs via a kinin- dependent mechanism. ACEI-related angioedema not only can start years after beginning the treatment, but it can then recur irregularly while under that treatment. Furthermore, allergy tests are unreliable for the diagnosis of ACEI-related angioedema, and so the relationship between angioedema and ACEIs is often missed and consequently quite underestimated. Accordingly, better understanding of the kinin-dependent mechanism, which is particular to angioedema, is necessary for the appropriate management of drug-induced angioedema.

Identification of a novel vga(E) gene variant that confers resistance to pleuromutilins, lincosamides and streptogramin A antibiotics in staphylococci of porcine origin.

Science.gov (United States)

Li, Jun; Li, Beibei; Wendlandt, Sarah; Schwarz, Stefan; Wang, Yang; Wu, Congming; Ma, Zhiyong; Shen, Jianzhong

2014-04-01

To investigate the genetic basis of pleuromutilin resistance in coagulase-negative staphylococci of porcine origin that do not carry known pleuromutilin resistance genes and to determine the localization and genetic environment of the identified resistance gene. Plasmid DNA of two pleuromutilin-resistant Staphylococcus cohnii and Staphylococcus simulans isolates was transformed into Staphylococcus aureus RN4220. The identified resistance plasmids were sequenced completely. The candidate gene for pleuromutilin resistance was cloned into shuttle vector pAM401. S. aureus RN4220 transformants carrying this recombinant shuttle vector were tested for their MICs. S. cohnii isolate SA-7 and S. simulans isolate SSI1 carried the same plasmid of 5584 bp, designated pSA-7. A variant of the vga(E) gene was detected, which encodes a 524 amino acid ATP-binding cassette protein. The variant gene shared 85.7% nucleotide sequence identity and the variant protein 85.3% amino acid sequence identity with the original vga(E) gene and Vga(E) protein, respectively. The Vga(E) variant conferred cross-resistance to pleuromutilins, lincosamides and streptogramin A antibiotics. Plasmid pSA-7 showed an organization similar to that of the apmA-carrying plasmid pKKS49 from methicillin-resistant S. aureus and the dfrK-carrying plasmid pKKS966 from Staphylococcus hyicus. Sequence comparisons suggested that recombination events may have played a role in the acquisition of this vga(E) variant. A novel vga(E) gene variant was identified, which was located on a small plasmid and was not associated with the transposon Tn6133 [in contrast to the original vga(E) gene]. The plasmid location may enable its further dissemination to other staphylococci and possibly also to other bacteria.

Effect of two active compounds obtained from the essential oil of Cordia verbenacea on the acute inflammatory responses elicited by LPS in the rat paw.

Science.gov (United States)

Medeiros, R; Passos, G F; Vitor, C E; Koepp, J; Mazzuco, T L; Pianowski, L F; Campos, M M; Calixto, J B

2007-07-01

alpha-Humulene and trans-caryophyllene are sesquiterpene compounds identified in the essential oil of Cordia verbenacea which display topical and systemic anti-inflammatory effects in different experimental models. However, the molecular mechanisms through which they exert their anti-inflammatory activity still remain unclear. Here, we evaluate the effects of alpha-humulene and trans-caryophyllene on the acute inflammatory responses elicited by LPS. The biological activities of alpha-humulene and trans-caryophyllene were investigated in a model of acute inflammation in rat paw, induced by LPS and characterized by paw oedema, neutrophil recruitment, cytokine production, activation of MAP kinases and NF-kappaB and up-regulated expression of kinin B(1) receptors. Treatment with either alpha-humulene or trans-caryophyllene effectively reduced neutrophil migration and activation of NF-kappaB induced by LPS in the rat paw. However, only alpha-humulene significantly reduced the increase in TNF-alpha and IL-1beta levels, paw oedema and the up-regulation of B(1) receptors following treatment with LPS. Both compounds failed to interfere with the activation of the MAP kinases, ERK, p38 and JNK. Both alpha-humulene and trans-caryophyllene inhibit the LPS-induced NF-kappaB activation and neutrophil migration, although only alpha-humulene had the ability to prevent the production of pro-inflammatory cytokines TNF-alpha and IL-1beta and the in vivo up-regulation of kinin B(1) receptors. These data provide additional molecular and functional insights into the beneficial effects of the sesquiterpenes alpha-humulene and trans-caryophyllene isolated from the essential oil of Cordia verbenacea as agents for the management of inflammatory diseases.

Hereditary angioedema.

Science.gov (United States)

Bracho, Francisco A

2005-11-01

Hereditary angioedema is an autosomal-dominant deficiency of C1 inhibitor--a serpin inhibitor of kallikrein, C1r, C1s, factor XII, and plasmin. Quantitative or qualitative deficiency of C1 inhibitor leads to the generation of vasoactive mediators, most likely bradykinin. The clinical syndrome is repeated bouts of nonpruritic, nonpitting edema of the face, larynx, extermities, and intestinal viscera. Recently, investigators, physicians, and industry have demonstrated a renewed interest in the biology and treatment of hereditary angioedema. Investigators have generated a C1INH-/- mouse model that has demonstrated the importance of the contact activation system for hereditary angioedema-related vascular permeability. An interactive database of mutations is available electronically. Investigators have continued exploration into mRNA/protein levels. The proceedings of a recent workshop have been impressive in the scope and depth. Clinicians have produced consensus documents and expert reviews. The pharmaceutical industry has initiated clinical trails with novel agents. Hereditary angioedema is often misdiagnosed and poorly treated. Diagnosis requires careful medical and family history and the measurement of functional C1 inhibitor and C4 levels. Attenuated androgens, anti-fibrinolytics, and C1 inhibitor concentrates are used for long-term and preprocedure prophylaxis, but have significant drawbacks. C1 inhibitor concentrates and fresh frozen plasma are available for acute intervention. The mainstays of supportive care are airway monitoring, pain relief, hydration, and control of nausea. New agents such as recombinant C1 inhibitor, kallikrein inhibitors, and bradykinin inhibitors may offer safer and more tolerable treatments.

A novel assay to diagnose hereditary angioedema utilizing inhibition of bradykinin-forming enzymes

DEFF Research Database (Denmark)

Joseph, Kusumam; Bains, Sonia; Tholanikunnel, Baby G

2015-01-01

. This was evident regardless whether we measured factor XIIa-C1-INH or kallikrein-C1-INH complexes, and the two assays were in close agreement. By contrast, testing the same samples utilizing the commercial method (complex ELISA, Quidel Corp.) revealed levels of C1-INH between 0 and 57% of normal (mean, 38%) and 42...

Evolution of an arsenal: structural and functional diversification of the venom system in the advanced snakes (Caenophidia).

Science.gov (United States)

Fry, Bryan G; Scheib, Holger; van der Weerd, Louise; Young, Bruce; McNaughtan, Judith; Ramjan, S F Ryan; Vidal, Nicolas; Poelmann, Robert E; Norman, Janette A

2008-02-01

Venom is a key innovation underlying the evolution of advanced snakes (Caenophidia). Despite this, very little is known about venom system structural diversification, toxin recruitment event timings, or toxin molecular evolution. A multidisciplinary approach was used to examine the diversification of the venom system and associated toxins across the full range of the approximately 100 million-year-old advanced snake clade with a particular emphasis upon families that have not secondarily evolved a front-fanged venom system ( approximately 80% of the 2500 species). Analysis of cDNA libraries revealed complex venom transcriptomes containing multiple toxin types including three finger toxins, cobra venom factor, cysteine-rich secretory protein, hyaluronidase, kallikrein, kunitz, lectin, matrix metalloprotease, phospholipase A(2), snake venom metalloprotease/a disintegrin and metalloprotease, and waprin. High levels of sequence diversity were observed, including mutations in structural and functional residues, changes in cysteine spacing, and major deletions/truncations. Morphological analysis comprising gross dissection, histology, and magnetic resonance imaging also demonstrated extensive modification of the venom system architecture in non-front-fanged snakes in contrast to the conserved structure of the venom system within the independently evolved front-fanged elapid or viperid snakes. Further, a reduction in the size and complexity of the venom system was observed in species in which constriction has been secondarily evolved as the preferred method of prey capture or dietary preference has switched from live prey to eggs or to slugs/snails. Investigation of the timing of toxin recruitment events across the entire advanced snake radiation indicates that the evolution of advanced venom systems in three front-fanged lineages is associated with recruitment of new toxin types or explosive diversification of existing toxin types. These results support the role of venom

Inhibitory effect of fentanyl citrate on the release of endothlin-1 induced by bradykinin in melanoma cells.

Science.gov (United States)

Andoh, Tsugunobu; Shinohara, Akira; Kuraishi, Yasushi

2017-02-01

Our previous study showed that the μ-opioid receptor agonist fentanyl citrate inhibits endothelin-1-and bradykinin-mediated pain responses in mice orthotopically inoculated with melanoma cells. We also demonstrated that bradykinin induces endothelin-1 secretion in melanoma cells. However, the analgesic mechanisms of fentanyl citrate remain unclear. Thus, the present study was conducted to determine whether fentanyl citrate affects bradykinin-induced endothelin-1 secretion in B16-BL6 melanoma cells. The amount of endothelin-1 in the culture medium was measured using an enzyme immunoassay. The expression of endothelin-1, kinin B 2 receptors, and μ-opioid receptors in B16-BL/6 melanoma cells was determined using immunocytochemistry. Fentanyl citrate inhibited bradykinin-induced endothelin-1 secretion. The inhibitory effect of fentanyl citrate on the secretion of endothelin-1 was attenuated by the μ-opioid receptor antagonist naloxone methiodide. The immunoreactivities of endothelin-1, kinin B 2 receptors, and μ-opioid receptors in B16-BL6 melanoma cells were observed. These results suggest that fentanyl citrate regulates bradykinin-induced endothelin-1 secretion through μ-opioid receptors in melanoma cells. Copyright © 2016 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

The stress response to surgery: release mechanisms and the modifying effect of pain relief

DEFF Research Database (Denmark)

Kehlet, H

1989-01-01

This short review updates information on the release mechanisms of the systemic response to surgical injury and the modifying effect of pain relief. Initiation of the response is primarily due to afferent nerve impulses combined with release of humoral substances (such as prostaglandins, kinins...... in releasing the classical endocrine catabolic response, while humoral factors are important for the hyperthermic response, changes in coagulation and fibrinolysis immunofunction, and capillary permeability. The modifying effect of pain relief on the surgical stress response is dependent upon the technique...... on the stress response. In summary, pain alleviation itself may not necessarily lead to an important modification of the stress response, and a combined approach with inhibition of the neural and humoral release mechanisms is necessary for a pronounced inhibition or prevention of the response to surgical injury....

Expression and regulation of murine SPINK12, a potential orthologue of human LEKTI2

Czech Academy of Sciences Publication Activity Database

Reiss, K.; Meyer-Hoffert, U.; Fischer, J.; Sperrhacke, M.; Wu, Z.; Dimitrieva, O.; Křenek, Pavel; Suchanová, Šárka; Buryová, Halka; Brauer, Rena; Sedláček, Radislav

2011-01-01

Roč. 20, č. 11 (2011), s. 905-910 ISSN 0906-6705 R&D Projects: GA ČR GC301/08/J053 Grant - others:Deutsche Forschungsgemeinschaft (DFG)(DE) Me2037/3-1 Institutional research plan: CEZ:AV0Z50520514 Keywords : epidermis * inhibitor * kallikrein * serine protease * spink Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.543, year: 2011

Blood coagulation factor XII drives adaptive immunity during neuroinflammation via CD87-mediated modulation of dendritic cells

Science.gov (United States)

Göbel, Kerstin; Pankratz, Susann; Asaridou, Chloi-Magdalini; Herrmann, Alexander M.; Bittner, Stefan; Merker, Monika; Ruck, Tobias; Glumm, Sarah; Langhauser, Friederike; Kraft, Peter; Krug, Thorsten F.; Breuer, Johanna; Herold, Martin; Gross, Catharina C.; Beckmann, Denise; Korb-Pap, Adelheid; Schuhmann, Michael K.; Kuerten, Stefanie; Mitroulis, Ioannis; Ruppert, Clemens; Nolte, Marc W.; Panousis, Con; Klotz, Luisa; Kehrel, Beate; Korn, Thomas; Langer, Harald F.; Pap, Thomas; Nieswandt, Bernhard; Wiendl, Heinz; Chavakis, Triantafyllos; Kleinschnitz, Christoph; Meuth, Sven G.

2016-01-01

Aberrant immune responses represent the underlying cause of central nervous system (CNS) autoimmunity, including multiple sclerosis (MS). Recent evidence implicated the crosstalk between coagulation and immunity in CNS autoimmunity. Here we identify coagulation factor XII (FXII), the initiator of the intrinsic coagulation cascade and the kallikrein–kinin system, as a specific immune cell modulator. High levels of FXII activity are present in the plasma of MS patients during relapse. Deficiency or pharmacologic blockade of FXII renders mice less susceptible to experimental autoimmune encephalomyelitis (a model of MS) and is accompanied by reduced numbers of interleukin-17A-producing T cells. Immune activation by FXII is mediated by dendritic cells in a CD87-dependent manner and involves alterations in intracellular cyclic AMP formation. Our study demonstrates that a member of the plasmatic coagulation cascade is a key mediator of autoimmunity. FXII inhibition may provide a strategy to combat MS and other immune-related disorders. PMID:27188843

The involvement of proteoglycans in the human plasma prekallikrein interaction with the cell surface.

Directory of Open Access Journals (Sweden)

Camila Lopes Veronez

Full Text Available INTRODUCTION: The aim of this work was to evaluate the role of human plasma prekallikrein assembly and processing in cells and to determine whether proteoglycans, along with high molecular weight kininogen (H-kininogen, influence this interaction. METHODS: We used the endothelial cell line ECV304 and the epithelial cell lines CHO-K1 (wild type and CHO-745 (deficient in proteoglycans. Prekallikrein endocytosis was studied using confocal microscopy, and prekallikrein cleavage/activation was determined by immunoblotting using an antibody directed to the prekallikrein sequence C364TTKTSTR371 and an antibody directed to the entire H-kininogen molecule. RESULTS: At 37°C, prekallikrein endocytosis was assessed in the absence and presence of exogenously applied H-kininogen and found to be 1,418.4±0.010 and 1,070.3±0.001 pixels/cell, respectively, for ECV304 and 1,319.1±0.003 and 631.3±0.001 pixels/cell, respectively, for CHO-K1. No prekallikrein internalization was observed in CHO-745 in either condition. Prekallikrein colocalized with LysoTracker in the absence and presence of exogenous H-kininogen at levels of 76.0% and 88.5%, respectively, for ECV304 and at levels of 40.7% and 57.0%, respectively, for CHO-K1. After assembly on the cell surface, a plasma kallikrein fragment of 53 kDa was predominant in the incubation buffer of all the cell lines studied, indicating specific proteolysis; plasma kallikrein fragments of 48-44 kDa and 34-32 kDa were also detected in the incubation buffer, indicating non-specific cleavage. Bradykinin free H-kininogen internalization was not detected in CHO-K1 or CHO-745 cells at 37°C. CONCLUSION: The prekallikrein interaction with the cell surface is temperature-dependent and independent of exogenously applied H-kininogen, which results in prekallikrein endocytosis promoted by proteoglycans. Prekallikrein proteolysis/activation is influenced by H-kininogen/glycosaminoglycans assembly and controls plasma kallikrein

Fracture mechanics based assessment of postulated flaws in the nozzle region of RPV-KKS under loss of coolant accidents; Bruchmechanische Bewertung von postulierten Fehlern im Stutzenbereich des RDB-KKS bei Kuehlmittelverlust-Stoerfaellen

Energy Technology Data Exchange (ETDEWEB)

Siegele, D.; Hodulak, L.; Varfolomeyev, I. [Fraunhofer-Institut fuer Werkstoffmechanik (IWM), Freiburg im Breisgau (Germany); Nagel, G. [Preussen Elektra AG, Hannover (Germany). Hauptverwaltung

1998-11-01

Safety assessment of reactor components has to encompass the nozzles, as in the event of a LOCA, the nozzle areas are subject to heavy thermal stresses due to the low temperature there of the cooling agent. The paper refers to three-dimensional, elasto-plastic FEM analyses of the integer RPV and calculations of the J-integral for various crack locations and geometries, for derivation of realistic transients. The J-integral and K values calculated with FEM have been compared with stress intensity factors determined by means of enhanced analytical methods. Calculations for description of the integer nozzle yield plastifications in the cladded and the ferritic areas, so that the K concept of linear-elastic fracture mechanics is restricted in applicability. For postulated cracks beneath the integer cladding, J-integral values are determined which are below the initiating value J{sub 1} of the material used, which excludes crack initiation. For the largest postulated, 20 mm deep surface crack and through-cladding damage, a crack growth of 0.1 mm is derived according to the crack resistance curve. The analytical method for calculating the stress intensity factors has been expanded to also include application to evaluation of nozzle edge cracks under the cladding. (orig./CB) [Deutsch] Bei der sicherheitstechnischen Bewertung von Reaktorkomponenten sind auch die Stutzen zu beruecksichtigen, da der Stutzenbereich bei Kuehlmittelverlust-Faellen, bedingt durch die dort vorliegenden tiefen Temperaturen des Kuehlmediums, hohen thermischen Beanspruchungen ausgesetzt ist. Fuer realistische Transienten werden dreidimensionale, elastisch-plastische FEM-Analysen fuer den integren RDB und Berechnungen des J-Integrals fuer verschiedene Risslagen und Rissgeometrien durchgefuehrt. Die mit FEM berechneten J-Integral- und K-Werte werden mit nach weiterentwickelten analytischen Methoden ermittelten Spannungsintensitaetsfatoren verglichen. Die Berechnungen fuer den integren Stutzen ergeben Plastifizierungen im Plattierungs- und im ferritischen Stutzenbereich, so dass das K-Konzept der linear-elastischen Bruchmechanik nur eingeschraenkt angewendet werden kann. Fuer postulierte Risse unter der intakten Plattierung werden J-Integral-Werte ermittelt, die unter dem Initiierungswert J{sub i} des eingesetzten Werkstoffs liegen, so dass eine Rissinitiierung ausgeschlossen ist. Fuer den groessten postulierten, 20 mm tiefen Oberflaechenriss bei durchtrennter Plattierung wird entsprechend der Risswiderstandskurve ein Risswachstum von ca. 0,1 mm ermittelt. Die analytische Methode zur Berechnung von Spannungsintensitaetsfaktoren wurde auf die Behandlung von Stutzenkantenrissen unter der Plattierung erweitert. (orig.)

Contact activation: a revision.

Science.gov (United States)

Schmaier, A H

1997-07-01

In conclusion, a revised view of the contact system has been presented. This system has little to do with the initiation of hemostasis. Like lupus anticoagulants, deficiencies of contact proteins give prolonged APTTs but may be risk factors for thrombosis. BK from kininogens is a potent modulator of vascular biology inducing vasodilation, tissue plasminogen activator release, and prostacyclin liberation. Kininogens, themselves, are selective inhibitors of alpha-thrombin-induced platelet activation preventing alpha-thrombin from cleaving the cloned thrombin receptor after arginine41. Kininogens' alpha-thrombin inhibitory activity exists in intact kininogens, BK, and all of BK's breakdown products. HK also is the pivotal protein for contact protein assembly on endothelium. It is the receptor for prekallikrein which when bound to HK becomes activated to kallikrein by an endothelial cell enzyme system independent of activated forms of plasma factor XII. Prekallikrein activation on endothelial cells results in kinetically favorable single chain urokinase and plasminogen activation. Thus the "physiologic, negatively charged surface" for contact system activation is really the assembly of these proteins on cell membranes and activation by membrane-associated enzymes.

Analytical one-dimensional frequency response and stability model for PWR nuclear power plants

International Nuclear Information System (INIS)

Hoeld, A.

1975-01-01

A dynamic model for PWR nuclear power plants is presented. The plant is assumed to consist of one-dimensional single-channel core, a counterflow once-through steam generator (represented by two nodes according to the nonboiling and boiling region) and the necessary connection coolant lines. The model describes analytically the frequency response behaviour of important parameters of such a plant with respect to perturbations in reactivity, subcooling or mass flow (both at the entrances to the reactor core and/or the secondary steam generator side), the perturbations in steam load or system pressure (on the secondary side of the steam generator). From corresponding 'open' loop considerations it can then be concluded - by applying the Nyquist criterion - upon the degree of the stability behaviour of the underlying system. Based on this theoretical model, a computer code named ADYPMO has been established. From the knowledge of the frequency response behaviour of such a system, the corresponding transient behaviour with respect to a stepwise or any other perturbation signal can also be calculated by applying an appropriate retransformation method, e.g. by using digital code FRETI. To demonstrate this procedure, a transient experimental curve measured during the pre-operational test period at the PWR nuclear power plant KKS Stade was recalculated using the combination ADYPMO-FRETI. Good agreement between theoretical calculations and experimental results give an insight into the validity and efficiency of the underlying theoretical model and the applied retransformation method. (Auth.)

Cardiovascular effects of intrathecally administered bradykinin in the rat: characterization of receptors with antagonists.

OpenAIRE

Lopes, P.; Regoli, D.; Couture, R.

1993-01-01

1. The effects of intrathecal (i.t.) pretreatment with selective B1 or B2 kinin receptor antagonists were studied on the cardiovascular response to i.t. injection of bradykinin (BK) in conscious freely moving rats. 2. BK (81 pmol) produced an increase in mean arterial pressure (MAP: 9-13 mmHg) and decrease in heart rate (HR: 20-30 beats min-1) that reached a maximum 2 min after injection. 3. The BK-induced cardiovascular responses were dose-dependently and reversibly reduced by four antagonis...

Optimum Use of Acute Treatments for Hereditary Angioedema: Evidence-Based Expert Consensus

OpenAIRE

Hilary Longhurst

2018-01-01

Acute treatment of hereditary angioedema due to C1 inhibitor deficiency has become available in the last 10 years and has greatly improved patients’ quality of life. Two plasma-derived C1 inhibitors (Berinert and Cinryze), a recombinant C1 inhibitor (Ruconest/Conestat alpha), a kallikrein inhibitor (Ecallantide), and a bradykinin B2 receptor inhibitor (Icatibant) are all effective. Durably good response is maintained over repeated treatments and several years. All currently available prophyla...

An Application About the Relationship Between Whistleblowing and Ethical Climate Ahlaki Olmayan Davranışların Duyurulması (Whistleblowing ve Etik İklimi İlişkisi Üzerine Bir Uygulama

Directory of Open Access Journals (Sweden)

Sahra SAYGAN

2013-09-01

Full Text Available Whistleblowing can be defined as revealing non-ethical events or behaviors (likeproducing harmful foods even though marketing them as they are remedial in anorganization. Organizational Ethical Climate is the second concept used in this work. Itconsists of workers’ opinions about the ethical organizational culture of management. Inthis work the relationship between “whistleblowing” and “ethical climate” is searched.The questionnaire used to evaluate the relationship between whistleblowing and ethicalclimate are applied on 123 research assistants in public universities. In the applicationstudy it’s reached that there is not a significant relationship between whistleblowing andethical climate. Even though it’s found that there is not a significant relationship between“whistleblowing” and “ethical climate”; a small significant relationship is discoveredbetween “whistleblowing” and “benevolent ethical climate”.Ahlaki olmayan davranışların duyurulması (Whistleblowing, bir işletmedeki etikolmayan davranış ve olayların açığa çıkarılması olarak tanımlanabilir. Etik iklim iseçalışanların örgüt kültürünün etiksel boyutuyla ilgili gözlem ve görüşlerindenoluşmaktadır. Bu çalışma, ‘Ahlaki olmayan davranışların duyurulması’ ve ‘Etik iklim’arasında anlamlı bir ilişkinin mevcut olup olmadığını araştırmaktadır. ‘Ahlaki olmayandavranışların duyurulması’ ve ‘Etik iklim’ arasındaki ilişkiyi ölçmek için kullanılan anketçalışması devlet üniversitelerindeki 123 araştırma görevlisi üzerinde uygulanmıştır.Uygulama çalışması neticesinde “Ahlaki olmayan davranışların duyurulması” ile “Etikİklim” arasında anlamlı bir ilişkinin bulunmamasına rağmen; etik iklim boyutlarından biriolan “Yardımsever Etik İklim” ile “Ahlaki olmayan davranışların duyurulması” arasındaanlamlı bir ilişkinin mevcut olduğu sonucuna ulaşılmıştır.

A repertoire of the dominant transcripts from the salivary glands of the blood-sucking bug, Triatoma dimidiata, a vector of Chagas disease

Science.gov (United States)

Kato, Hirotomo; Jochim, Ryan C.; Gomez, Eduardo A.; Sakoda, Ryo; Iwata, Hiroyuki; Valenzuela, Jesus G.; Hashiguchi, Yoshihisa

2010-01-01

Triatoma (T.) dimidiata is a hematophagous Hemiptera and a main vector of Chagas disease. The saliva of this and other blood-sucking insects contains potent pharmacologically active components that assist them in counteracting the host hemostatic and inflammatory systems during blood feeding. To describe the repertoire of potential bioactive salivary molecules from this insect, a number of randomly selected transcripts from the salivary gland cDNA library of T. dimidiata were sequenced and analyzed. This analysis showed that 77.5% of the isolated transcripts coded for putative secreted proteins, and 89.9% of these coded for variants of the lipocalin family proteins. The most abundant transcript was a homologue of procalin, the major allergen of T. protracta saliva, and contributed more than 50% of the transcripts coding for putative secreted proteins, suggesting that it may play an important role in the blood-feeding process. Other salivary transcripts encoding lipocalin family proteins had homology to triabin (a thrombin inhibitor), triafestin (an inhibitor of kallikrein–kinin system), pallidipin (an inhibitor of collagen-induced platelet aggregation) and others with unknown function. PMID:19900580

Biomarkers for Early Detection of Clinically Relevant Prostate Cancer: A Multi-Institutional Validation Trial

Science.gov (United States)

2015-10-01

biomarkers; prediction models; PCA3; TMPRSS2: ERG ; kallikreins; 4KScore; OncotypeDX; 5 3. ACCOMPLISHMENTS What were the major goals and...urine, alone or in combination with TMPRSS2: ERG mRNA. (Lead site: FHCRC) Milestone 10. Urine specimens identified for analysis. Due 12/30/2014...COMPLETED Milestone 11. PCA3 and TMPRSS2: ERG validation complete in PASS cohort. Due 12/30/2015 Milestone 12. Manuscript submission of PCA3 and TMPRSS2: ERG

A cytotoxic serine proteinase isolated from mouse submandibular gland.

Science.gov (United States)

Shimamura, T; Nagumo, N; Ikigai, H; Murakami, K; Okubo, S; Toda, M; Ohnishi, R; Tomita, M

1989-08-01

We have isolated a novel cytotoxic factor from the submandibular glands of male BALB/c mice by Sephadex G-50 gel filtration chromatography and reverse-phase HPLC. The cytotoxic factor is a serine proteinase, which belongs to the mouse glandular kallikrein (mGK) family, with an Mr of approximately 27,000. The purified serine proteinase showed cytotoxic activity against mouse thymocytes in a dose-dependent manner, and a serine proteinase inhibitor, diisopropyl fluorophosphate, blocked its cytotoxic activity.

Plasmin substrate binding site cooperativity guides the design of potent peptide aldehyde inhibitors.

Science.gov (United States)

Swedberg, Joakim E; Harris, Jonathan M

2011-10-04

Perioperative bleeding is a cause of major blood loss and is associated with increased rates of postoperative morbidity and mortality. To combat this, antifibrinolytic inhibitors of the serine protease plasmin are commonly used to reduce bleeding during surgery. The most effective and previously widely used of these is the broad range serine protease inhibitor aprotinin. However, adverse clinical outcomes have led to use of alternative serine lysine analogues to inhibit plasmin. These compounds suffer from low selectivity and binding affinity. Consequently, a concerted effort to discover potent and selective plasmin inhibitors has developed. This study used a noncombinatorial peptide library to define plasmin's extended substrate specificity and guide the design of potent transition state analogue inhibitors. The various substrate binding sites of plasmin were found to exhibit a higher degree of cooperativity than had previously been appreciated. Peptide sequences capitalizing on these features produced high-affinity inhibitors of plasmin. The most potent of these, Lys-Met(sulfone)-Tyr-Arg-H [KM(O(2))YR-H], inhibited plasmin with a K(i) of 3.1 nM while maintaining 25-fold selectivity over plasma kallikrein. Furthermore, 125 nM (0.16 μg/mL) KM(O(2))YR-H attenuated fibrinolysis in vitro with an efficacy similar to that of 15 nM (0.20 μg/mL) aprotinin. To date, this is the most potent peptide inhibitor of plasmin that exhibits selectivity against plasma kallikrein, making this compound an attractive candidate for further therapeutic development.

KLK5 and KLK7 Ablation Fully Rescues Lethality of Netherton Syndrome-Like Phenotype

Czech Academy of Sciences Publication Activity Database

Kašpárek, Petr; Ileninová, Zuzana; Žbodáková, Olga; Kanchev, Ivan; Benada, Oldřich; Chalupský, Karel; Brattsand, M.; Beck, Inken; Sedláček, Radislav

2017-01-01

Roč. 13, č. 1 (2017), č. článku e1006566. ISSN 1553-7404 R&D Projects: GA MŠk(CZ) ED1.1.00/02.0109; GA MŠk(CZ) LQ1604; GA MŠk(CZ) LM2011032; GA MŠk(CZ) LO1509 Institutional support: RVO:68378050 ; RVO:61388971 Keywords : corneum chymotryptic enzyme * serine-protease inhibitor * skin barrier function * mouse model * hair-follicle * subtilisin-a * lekti * kallikrein * expression * mice Subject RIV: EB - Genetics ; Molecular Biology; EE - Microbiology, Virology (MBU-M) OBOR OECD: Microbiology Impact factor: 6.100, year: 2016

Autoradiographic studies of the pancreas and adrenal cortex with 3H-thymidine, age dependence and other influencing factors

International Nuclear Information System (INIS)

Izbirak, C.D.

1979-01-01

The cell proliferation of pancreatic and corticoadrenal cells and their susceptibility towards exogenically administered kallikrein and isoprenalin was studied with the aid of 3 H-thymidine autoradiography. It can be assumed that those cells tabelled with 3 H-thymidine within the time available and which after pooling, served as labelling index also included those undergoing DNA synthesis in the mitotic phase and which therefore also join in cell proliferation. This investigation is based on material generated from 28 black mice of the strain C 57. (orig./MG) [de

Urinary prostaglandin E and vasopressin excretion in essential fatty acid-deficient rats

DEFF Research Database (Denmark)

Hansen, Harald S.; Jensen, B.

1983-01-01

excretion of prostaglandin E (PGE), immunoreactive arginine vasopressin (iA VP), and kallikrein were determined. PGE was quantitated with a radioimmunoassay having 4.9% cross-reactivity with prostaglandin E (PGE). After 4 weeks on the diet, water consumption and urinary iAVP excretion increased....... Increased water consumption and increased urinary iAVP excretion seem to be early symptoms (after 4 weeks) of EFA deficiency, whereas decreased urine output and decreased urinary PGE excretion occur much later (after 10 weeks). Two energy% linolenate supplementation to a fat-free diet did not change...

The C-terminal sequence of several human serine proteases encodes host defense functions.

Science.gov (United States)

Kasetty, Gopinath; Papareddy, Praveen; Kalle, Martina; Rydengård, Victoria; Walse, Björn; Svensson, Bo; Mörgelin, Matthias; Malmsten, Martin; Schmidtchen, Artur

2011-01-01

Serine proteases of the S1 family have maintained a common structure over an evolutionary span of more than one billion years, and evolved a variety of substrate specificities and diverse biological roles, involving digestion and degradation, blood clotting, fibrinolysis and epithelial homeostasis. We here show that a wide range of C-terminal peptide sequences of serine proteases, particularly from the coagulation and kallikrein systems, share characteristics common with classical antimicrobial peptides of innate immunity. Under physiological conditions, these peptides exert antimicrobial effects as well as immunomodulatory functions by inhibiting macrophage responses to bacterial lipopolysaccharide. In mice, selected peptides are protective against lipopolysaccharide-induced shock. Moreover, these S1-derived host defense peptides exhibit helical structures upon binding to lipopolysaccharide and also permeabilize liposomes. The results uncover new and fundamental aspects on host defense functions of serine proteases present particularly in blood and epithelia, and provide tools for the identification of host defense molecules of therapeutic interest. Copyright © 2011 S. Karger AG, Basel.

EXPRESSION OF NOVEL TYPES OF MYTHOLOGY AUTHORITY REFLECTION ON MANAGEMENT MİTOLOJİDEN ROMANA YÖNETİM ERKİNİN ANLATIM TÜRLERİNE YANSIMASI

Directory of Open Access Journals (Sweden)

Kürşat ÖNCÜL

2010-01-01

Full Text Available The main subject , is a based on a review of the product in the narration, a sense of social life depends historical progress. This acceptance, the mythological history of civilization of the human race, religious and scientific thought system operates similar to the arguments in view of the described products and has developed a form born in the defense. However, the relationship between species, also shows the relationship between individuals and management. Anlatma esasına dayalı ürünlerin incelenmesinde, sosyal yaşama bağlı tarihsel ilerlemeci bir anlayış, söz konusudur. Bu kabul, insan ırkının uygarlık tarihinin mitolojik, dini ve bilimsel bir düşünüş sistemi izlediği savından hareketle anlatı ürünlerinin de benzer bir formda doğup geliştiğini savunur. Ancak türler arasındaki ilişki birey ile yönetim arasındaki ilişkinin de göstergesidir.

Design and synthesis of novel sulfonamide-containing bradykinin hB2 receptor antagonists. 2. Synthesis and structure-activity relationships of alpha,alpha-cycloalkylglycine sulfonamides.

Science.gov (United States)

Fattori, Daniela; Rossi, Cristina; Fincham, Christopher I; Caciagli, Valerio; Catrambone, Fernando; D'Andrea, Piero; Felicetti, Patrizia; Gensini, Martina; Marastoni, Elena; Nannicini, Rossano; Paris, Marielle; Terracciano, Rosa; Bressan, Alessandro; Giuliani, Sandro; Maggi, Carlo A; Meini, Stefania; Valenti, Claudio; Quartara, Laura

2007-02-08

Recently we reported on the design and synthesis of a novel class of selective nonpeptide bradykinin (BK) B2 receptor antagonists (J. Med. Chem. 2006, 3602-3613). This work led to the discovery of MEN 15442, an antagonist with subnanomolar affinity for the human B2 receptor (hB2R), which also displayed significant and prolonged activity in vivo (for up to 210 min) against BK-induced bronchoconstriction in the guinea-pig at a dose of 300 nmol/kg (it), while demonstrating only a slight effect on BK-induced hypotension. Here we describe the further optimization of this series of compounds aimed at maximizing the effect on bronchoconstriction and minimizing the effect on hypotension, with a view to developing topically delivered drugs for airway diseases. The work led to the discovery of MEN 16132, a compound which, after intratracheal or aerosol administration, inhibited, in a dose-dependent manner, BK-induced bronchoconstricton in the airways, while showing minimal systemic activity. This compound was selected as a preclinical candidate for the topical treatment of airway diseases involving kinin B2 receptor stimulation.

Comparative temporospatial expression profiling of murine amelotin protein during amelogenesis.

Science.gov (United States)

Somogyi-Ganss, Eszter; Nakayama, Yohei; Iwasaki, Kengo; Nakano, Yukiko; Stolf, Daiana; McKee, Marc D; Ganss, Bernhard

2012-01-01

Tooth enamel is formed in a typical biomineralization process under the guidance of specific organic components. Amelotin (AMTN) is a recently identified, secreted protein that is transcribed predominantly during the maturation stage of enamel formation, but its protein expression profile throughout amelogenesis has not been described in detail. The main objective of this study was to define the spatiotemporal expression profile of AMTN during tooth development in comparison with other known enamel proteins. A peptide antibody against AMTN was raised in rabbits, affinity purified and used for immunohistochemical analyses on sagittal and transverse paraffin sections of decalcified mouse hemimandibles. The localization of AMTN was compared to that of known enamel proteins amelogenin, ameloblastin, enamelin, odontogenic ameloblast-associated/amyloid in Pindborg tumors and kallikrein 4. Three-dimensional images of AMTN localization in molars at selected ages were reconstructed from serial stained sections, and transmission electron microscopy was used for ultrastructural localization of AMTN. AMTN was detected in ameloblasts of molars in a transient fashion, declining at the time of tooth eruption. Prominent expression in maturation stage ameloblasts of the continuously erupting incisor persisted into adulthood. In contrast, amelogenin, ameloblastin and enamelin were predominantly found during the early secretory stage, while odontogenic ameloblast-associated/amyloid in Pindborg tumors and kallikrein 4 expression in maturation stage ameloblasts paralleled that of AMTN. Secreted AMTN was detected at the interface between ameloblasts and the mineralized enamel. Recombinant AMTN protein did not mediate cell attachment in vitro. These results suggest a primary role for AMTN in the late stages of enamel mineralization. Copyright © 2011 S. Karger AG, Basel.

Immunochemical studies of yellowjacket venom proteins.

Science.gov (United States)

King, T P; Alagon, A C; Kuan, J; Sobotka, A K; Lichtenstein, L M

1983-03-01

The major proteins of yellowjacket venoms have been isolated and characterized immuno-chemically. They consist of hyaluronidase, phospholipase, and antigen 5. Venoms from three species of yellowjacket were studied. Vespula germanica, V. maculifrons, and V. vulgaris. The phospholipases could be isolated in good yield only when affinity chromatography was used to minimize limited proteolysis. A kallikrein-like peptidase was found present in the yellowjacket venom. Phospholipases from these three species were immunochemically indistinguishable from each other, as were their antigen 5s. Sera from individuals sensitive to yellowjacket venom contained IgE and IgG specific for antigen 5 and phospholipase.

Identification of genetic factors associated with susceptibility to angiotensin-converting enzyme inhibitors-induced cough.

Science.gov (United States)

Grilo, Antonio; Sáez-Rosas, María P; Santos-Morano, Juan; Sánchez, Elena; Moreno-Rey, Concha; Real, Luis M; Ramírez-Lorca, Reposo; Sáez, María E

2011-01-01

Angiotensin-converting enzyme inhibitors (ACEi) are the first selected drugs for hypertensive patients because of its protective properties against heart and kidney diseases. Persistent cough is a common adverse reaction associated with ACEi, which can bind to the treatment cessation, but its etiology remains an unresolved issue. The most accepted mechanism is that the inhibition of ACEi increases kinins levels, resulting in the activation of proinflammatory mechanisms and nitric oxide generation. However, relatively little is known about the genetic susceptibility to ACEi-induced cough in hypertensive patients. We carried out a monogenic association analysis of 39 polymorphisms and haplotypes in genes encoding key proteins related to ACEi activity with the occurrence of ACEi-induced cough. We also carried out a digenic association analysis and investigated the existence of epistatic interactions between the analyzed polymorphisms using a logistic regression procedure. Finally, we investigated the predictive value of the identified associations for ACEi-induced cough. We found that genetic polymorphisms in MME [rs2016848, P=0.002, odds ratio (OR)=1.795], BDKRB2 (rs8012552, P=0.012, OR=1.609), PTGER3 (rs11209716, P=0.002, OR=0.565), and ACE (rs4344) genes are associated with ACEi-related cough. For the latter, the effect is sex specific, having a protective effect in males (P=0.027, OR=0.560) and increasing the risk in females (P=0.031, OR=1.847). In addition, genetic interactions between peptidases involved in kinins levels (CPN1 and XPNPEP1) and proteins related to prostaglandin metabolism (PTGIS and PTGIR) strongly modify the risk of ACEi-induced cough presentation (0.102≤OR≤0.384 for protective combinations and 2.732≤OR≤7.216 for risk combinations). These results are consistent with the hypothesis that the mechanism of cough is related to the accumulation of bradykinin, substance P, and prostaglandins.

TURİST REHBERLERİNİN MOTİVASYONU İLE PERFORMANSI ARASINDAKİ İLİŞKİNİN BELİRLENMESİ

OpenAIRE

KÖROĞLU, ÖZLEM; AVCIKURT, CEVDET

2015-01-01

Turist rehberlerinin performans düzeylerinin ölçülmesi, rehberlerin motivasyonu ile performansı arasında herhangi bir ilişkinin bulunup bulunmadığının tespit edilmesi ve turist rehberlerinin demografik değişkenleri ile motivasyonu ve performansı arasındaki ilişkilerin belirlenmesi bu çalışmanın amacını oluşturmaktadır. Elde edilen kuramsal bilgilere dayanarak araştırma hipotezi belirlenmiş ve araştırma modeli geliştirilmiştir. Verilerin elde edilmesi için anket tekniği kullanılarak turist reh...

Selective kallikrein inhibitors alter human neutrophil elastase release during extracorporeal circulation

NARCIS (Netherlands)

Wachtfogel, Y.T.; Hack, C.E.; Nuijens, J.H; Kettner, C.; Reilly, T.M.; Knabb, R.M.; Bischoff, Rainer; Tschesche, H.; Wenzel, H.; Kucich, U.

1995-01-01

Cardiopulmonary bypass causes hemorrhagic complications and initiates a biochemical and cellular "whole body inflammatory response." This study investigates whether a variety of selective inhibitors of the contact pathway of intrinsic coagulation modulate complement and neutrophil activation during

Investigations of the detection of α-radioactivity in samples of effluent water primary circuit and exhaust air of nuclear power plants in the FRG in the years 1973-1975

International Nuclear Information System (INIS)

Hoetzl, H.; Rosner, G.; Winkler, R.

1976-05-01

Since the middle of 1973 the α-radioactivity of aerosol filters from the stack monitoring system and since the middle of 1974 the α-radioactivity in samples from the primary cycle of the KRB was monitored. Effluent water samples of all nuclear power reactors of the FRG were also examined from the middle of 1973 till 1974. Furthermore, aerosol filters sampled in 1973 and 1974 from various places at the KRB and some aerosol filters from the stack monitoring systems of KWW (1973), KWO (1974) and KKS (1975) were also measured. Essentially, the following procedures of sample preparation for α-spectrometry of the samples in large-area gridded ionization chambers were used: cold ashing of the aerosol samples in 'excited' oxygen; coprecipitation of the alpha emitters from the effluent water samples with iron hydroxide and subsequent cold ashing of the precipitate; evaporation of the samples from the primary cycle on SS plates. The following transuranium nuclides, or some of them, were found in the samples of the primary coolant and in several aerosol filter samples: Pu-239/240, Pu-238 and/or Am-241, Cm-242 and Cm-244. Cm-242 contributes most to the α-radioactivity in fresh samples. In the effluent water samples Cm-242. Pu-239/240 and Pu-238 and/or Am-241 were identified in some cases, in one case also Cm-244. The aim of these investigations is to establish procedures for the measurement and surveillance of α-emitting nuclides in the emissions of power reactors in order to study the contribution of transuranium nuclides to the radiation exposure of the population living in the vicinity of nuclear power stations. (orig.) [de

Chemiluminescence response of whole blood and separated blood cells in cases of experimentally induced pancreatitis and MDTQ-DA-Trasylol-ascorbic acid therapy

Energy Technology Data Exchange (ETDEWEB)

Zimmermann, T.; Schuster, R.; Lauschke, G.; Trausch, M. (Medical Academy of Dresden (Germany). Department of Surgery); Albrecht, S. (Medical Academy of Dresden (Germany). Institute of Clinical Chemistry); Kopprasch, S.; Kuehne, H. (Medical Academy of Dresden (Germany). Institute of Pathological Biochemistry)

1991-12-24

The formation of reactive O{sub 2} species in the pancreas of pigs after induction of necrotizing or oedematous pancreatitis was studied by means of luminol- and lucigenin-sensitized chemiluminescence. The effect of 2,2-dimethyl-4-methanesulphonic acid-1,2-dihydroquinoline in combination with Trasylol and ascorbic acid was studied in vivo. This combined therapy leads to a reduction in the chemiluminescence response by 50-70% with prevention of pancreatogenic shock and multiple organ failure by improvement of the gluthathione status. A combination of radical traps, kallikrein inhibitors and natural antioxidative sub-stances is an efficient alternative therapy in cases of acute pancrea-titis. (author). 10 refs.; 5 figs.

GİRİŞİMCİLİKTE KİŞİLİK ÖZELLİKLERİ BELİRLEYİCİ MİDİR?

OpenAIRE

Keskin, Gulseren; Tasdemir, Gulay; Aktekin, Elif; Gumussoy, Sureyya

2016-01-01

Son zamanlarda girişimcilik ekonomik büyüme ve istihdam yaratılmasında önemli bir kavram olarak dikkati çekmektedir. İnsan faktörü girişimcilikte başta değerlendirilmesi gereken yapıdır. Bu çalışmada girişimcilikle bireysel kişilik özelikleri arasındaki ilişkinin incelenmesi amaçlanmıştır. Pubmed, Medline, EBSCOHost, PsycINFO, Türk Medline veri tabanlarında ve Google Akademik’te yer alan girişimcilik, kişilik gibi anahtar kelimeler kullanılarak ilgili makaleler taranmış ve gözden geçirme için...

Dispeptik yakınmalı hastaların dental plak ve mide biyopsi örneklerinde helicobacter pylori'nin real Time-PCR ile araştırılması

OpenAIRE

Altındiş, Selma; Altındiş, Mustafa; Özdemir, Müjgan; Ellidokuz, Ender; Uslan, İhsan; Duran, İsmet; Dilek, Hüsniye

2010-01-01

Helicobacter pylori, kronik gastritin ana nedeni olup gastrik ve duodenal ulser gelişmesinde de rolü vardır. Dental plak, H.pylori için bir rezervuar olabilir fakat ağız mikroflorasının H.pylori için kalıcı bir rezervuar olduğu hipotezi hala tartışılmaktadır. Bu çalışmada, Dispeptik yakınmalı populasyonda, mide antrum ve dental plaklarda Real Time-PCR yöntemi ile H.pylori DNA'sı varlığı ve bu enfeksiyon ile oral hijyen indeksi arasındaki ilişkinin araştırılması amaçlanmıştır.Dispeptik ya...

Protective effects of simvastatin on coronary artery function in swine with acute infection

DEFF Research Database (Denmark)

Liuba, Petru; Pesonen, Erkki; Forslid, Anders

2006-01-01

cholesterol) between the groups (p>0.2). CONCLUSION:: Acute infection is associated with impairment of the muscarinic and kinin-related reactivity of coronary circulation. These functional abnormalities are in part prevented by simvastatin through mechanisms unrelated to lipid lowering......BACKGROUND:: The risk for coronary events may rise during acute infection. Perturbation in coronary endothelial function emerges as one important link. We investigated whether simvastatin could protect the coronary arterial function from the adverse effects of acute infection in swine. METHODS......:: Coronary endothelium-dependent and -independent vasomotor responses were assessed by Doppler velocimetry in 12 Chlamydia pneumoniae-infected and 6 sham-infected swine 2 weeks after intratracheal inoculation. Half of animals from the infection group were pre-treated with simvastatin (80mg daily), while...

Essential hypertension in adolescents and children: Recent advances in causative mechanisms

Directory of Open Access Journals (Sweden)

Manu Raj

2011-01-01

Full Text Available Essential hypertension is the most common form of hypertension in adults, and it is recognized more often in adolescents than in younger children. It is well known that the probability of a diagnosis of essential hypertension increases with age from birth onward. The initiation of high blood pressure burden starts in childhood and continues through adolescence to persist in the remaining phases of life. The genesis of essential hypertension is likely to be multifactorial. Obesity, insulin resistance, activation of sympathetic nervous system, sodium homeostasis, renin-angiotensin system, vascular smooth muscle structure and reactivity, serum uric acid levels, genetic factors and fetal programming have been implicated in this disorder. In addition, erythrocyte sodium transport, the free calcium concentration in platelets and leukocytes, urine kallikrein excretion, and sympathetic nervous system receptors have also been investigated as other possible mechanisms. Obesity in children appears to be the lead contributor of essential hypertension prevalence in children and adolescents. Suggested mechanisms of obesity-related hypertension include insulin resistance, sodium retention, increased sympathetic nervous system activity, activation of renin-angiotensin-aldosterone, and altered vascular function. The etiopathogenesis of essential hypertension in children and adolescents appears to closely resemble that of adults. The minor variations seen could probably be due to the evolving nature of this condition. Many of the established mechanisms that are confirmed in adult population need to be replicated in the pediatric age group by means of definitive research for a better understanding of this condition in future.

Enzymatic assays for the diagnosis of bradykinin-dependent angioedema.

Directory of Open Access Journals (Sweden)

Federica Defendi

Full Text Available BACKGROUND: The kinins (primarily bradykinin, BK represent the mediators responsible for local increase of vascular permeability in hereditary angioedema (HAE, HAE I-II associated with alterations of the SERPING1 gene and HAE with normal C1-Inhibitor function (HAE-nC1INH. Besides C1-Inhibitor function and concentration, no biological assay of kinin metabolism is actually available to help physicians for the diagnosis of angioedema (AE. We describe enzymatic tests on the plasma for diagnosis of BK-dependent AE. METHODS: The plasma amidase assays are performed using the Pro-Phe-Arg-p-nitroanilide peptide substrate to evaluate the spontaneous amidase activity and the proenzyme activation. We analyzed data of 872 patients presenting with BK-dependent AE or BK-unrelated diseases, compared to 303 controls. Anti-high MW kininogen (HK immunoblot was achieved to confirm HK cleavage in exemplary samples. Reproducibility, repeatability, limit of blank, limit of detection, precision, linearity and receiver operating characteristics (ROC were used to calculate the diagnostic performance of the assays. RESULTS: Spontaneous amidase activity was significantly increased in all BK-dependent AE, associated with the acute phase of disease in HAE-nC1INH, but preserved in BK-unrelated disorders. The increase of the amidase activity was associated to HK proteolysis, indicating its relevance to identify kininogenase activity. The oestrogens, known for precipitating AE episodes, were found as triggers of enzymatic activity. Calculations from ROC curves gave the optimum diagnostic cut-off for women (9.3 nmol⋅min(-1⋅mL(-1, area under curve [AUC] 92.1%, sensitivity 80.0%, and specificity 90.1% and for men (6.6 nmol·min(-1⋅mL(-1, AUC 91.0%, sensitivity 87.0% and specificity 81.2%. CONCLUSION: The amidase assay represents a diagnostic tool to help physicians in the decision to distinguish between BK-related and -unrelated AE.

Halkın Genetiği Değiştirilmiş Ürünlere/Üretilme Süreçlerine Yönelik Algıları ve Etik İnançları

Directory of Open Access Journals (Sweden)

Özlen Özgen

2014-02-01

Full Text Available Bu araştırmanın amacı, halkın genetiği değiştirilmiş ürünlere ve üretilme süreçlerine yönelik fayda/risk algıları ile etik inançları arasındaki ilişkinin incelenmesidir. Araştırma materyalinin toplanmasında karşılıklı görüşme tekniği kullanılmıştır. Likert tipi cümlelere verilen yanıtlar puanlanmış, geçerlik ve güvenirlik analizi yapılmıştır. Yaş değişkenine bağlı farklılığın belirlenebilmesi için t-testi uygulanmıştır. Bireylerin genetiği değiştirilmiş ürünlere/üretilme süreçlerine bağlı fayda/risk algıları ile etik inançları arasındaki ilişkinin incelenmesi amacı ile Pearson korelasyon analizi yapılmıştır. Bulgular; tüketicilerin genetiği değiştirilmiş ürünlere ilişkin fayda algılarının, genetiği değiştirilmiş ürünlere ve üretilme süreçlerine ilişkin risk algılarının, genetiği değiştirilmiş ürünlere ve üretilme süreçlerine ilişkin etik inançlarının yaşa bağlı olarak değiştiğini göstermektedir. Pearson korelasyon analizi sonucunda p<0.001 düzeyinde anlamlı ilişkiler saptanmıştır.

Formation, clearance, deposition, pathogenicity, and identification of biopharmaceutical-related immune complexes: review and case studies.

Science.gov (United States)

Rojko, Jennifer L; Evans, Mark G; Price, Shari A; Han, Bora; Waine, Gary; DeWitte, Mark; Haynes, Jill; Freimark, Bruce; Martin, Pauline; Raymond, James T; Evering, Winston; Rebelatto, Marlon C; Schenck, Emanuel; Horvath, Christopher

2014-06-01

Vascular inflammation, infusion reactions, glomerulopathies, and other potentially adverse effects may be observed in laboratory animals, including monkeys, on toxicity studies of therapeutic monoclonal antibodies and recombinant human protein drugs. Histopathologic and immunohistochemical (IHC) evaluation suggests these effects may be mediated by deposition of immune complexes (ICs) containing the drug, endogenous immunoglobulin, and/or complement components in the affected tissues. ICs may be observed in glomerulus, blood vessels, synovium, lung, liver, skin, eye, choroid plexus, or other tissues or bound to neutrophils, monocytes/macrophages, or platelets. IC deposition may activate complement, kinin, and/or coagulation/fibrinolytic pathways and result in a systemic proinflammatory response. IC clearance is biphasic in humans and monkeys (first from plasma to liver and/or spleen, second from liver or spleen). IC deposition/clearance is affected by IC composition, immunomodulation, and/or complement activation. Case studies are presented from toxicity study monkeys or rats and indicate IHC-IC deposition patterns similar to those predicted by experimental studies of IC-mediated reactions to heterologous protein administration to monkeys and other species. The IHC-staining patterns are consistent with findings associated with generalized and localized IC-associated pathology in humans. However, manifestations of immunogenicity in preclinical species are generally not considered predictive to humans. © 2014 by The Author(s).

Inhibition of coagulation factors by recombinant barley serpin BSZx

DEFF Research Database (Denmark)

Dahl, Søren Weis; Rasmussen, S.K.; Petersen, L..C.

1996-01-01

Barley serpin BSZx is a potent inhibitor of trypsin and chymotrypsin at overlapping reactive sites (Dahl, S.W., Rasmussen, S.K. and Hejgaard, J. (1996) J. Biol, Chem., in press), We have now investigated the interactions of BSZx with a range of serine proteinases from human plasma, pancreas......, urokinase and tissue type plasminogen activator, plasmin and pancreas kallikrein and elastase were not or only weakly affected, The inhibition pattern with mammalian proteinases reveal a specificity of BSZx similar to that of antithrombin III. Trypsin from Fusarium was not inhibited while interaction...... with subtilisin Carlsberg and Novo was rapid but most BSZx was cleaved as a substrate, Identification of a monoclonal antibody specific for native BSZx indicate that complex formation and loop cleavage result in similar conformational changes....

ŞİDDET MAĞDURU KADINLARIN ERKEKLİK TANIMLAMALARI: BURDUR İLİ ÖZELİNDE BİR ÇALIŞMA - MASCULINITY DEFINITION OF WOMEN VICTIMS OF VIOLENCE: A CASE STUDY IN BURDUR, TURKEY

OpenAIRE

DEMEZ, Gönül; SEVAL, Hale Nur

2018-01-01

Buçalışmanın odağını,  fiziksel, sözel,cinsel şiddete maruz kalmış ve Burdur Aile ve Sosyal Politikalar İl Müdürlüğünebağlı Kadın Konukevi Müdürlüğü’nden hizmet almakta olan farklı (ekonomik durum,yaş, medeni durum, eğitim durumu) kategorilerden kadınların, toplumsal cinsiyetkalıpları anlamında erkeklik rollerine ilişkin anlamlandırma ve yargılarının ortayaçıkarılması; bu bağlamda şiddet deneyimleri ile erkeklik algıları arasındakiilişkinin irdelenmesi oluşturmaktadır. Yüz yüze derinlemesine ...

Anneden Allah'a: Bağlanma Teorisi ve İslâm'da Allah Tasavvuru

OpenAIRE

HAYTA, Akif

2006-01-01

John Bowlby tarafından geliştirilen bağlanma teorisi, yaşam boyu süren psikolojik bir sosyal ve kişilik gelişim teorisidir. Bağlanma teorisi bebek-çocuk ve bakıcısı arasındaki bağın gelişimi ve bu ilişkinin çeşitli fonksiyonlarının daha sonraki psikolojik gelişim üzerindeki etkilerine odaklanmıştır. Bağlanma teorisi bebek ve çocuk üzerine yapılan çalışmaları önemli derecede etkilemiş ve yığınla araştırmaya konu olmuştur. Aynı zamanda geniş bir alana yayılarak din psikolojisi araştırmalarında ...

TEDARİK ZİNCİRİ ENTEGRASYONU VE HASTA GÜVENLİĞİ İLİŞKİSİNİN ANALİZİ

OpenAIRE

Tütüncü, Özkan; Küçükusta, Deniz

2014-01-01

Çalışmanın amacı hastanede görev yapan sterilizasyon sorumlularının tedarik zinciri entegrasyonu ve hasta güvenliği kültürüne ilişkin algılarının belirlemesi ve aralarındaki ilişkinin analiz edilmesidir. Çalışmada, Gaziantep’te düzenlenen 2. Sterilizasyon Semineri’ne katılan Ege ve Güneydoğu Anadolu bölgeleri sterilizasyon sorumlularının algıları, yapılandırılmış anket tekniği kullanılarak analiz edilmiştir. Yapısal geçerliliği ölçmek için ölçeklere uygulanan faktör analizi ve güvenilirlik a...

Indomethacin can downregulate the levels of inflammatory mediators in the hippocampus of rats submitted to pilocarpine-induced status epilepticus

Directory of Open Access Journals (Sweden)

Michele Juliane Vieira

2014-09-01

Full Text Available OBJECTIVE: Refractory status epilepticus is one of the most life-threatening neurological emergencies and is characterized by high morbidity and mortality. Additionally, the use of anti-inflammatory drugs during this period is very controversial. Thus, this study has been designed to analyze the effect of a low dose of indomethacin (a COX inhibitor on the expression of inflammatory molecules. METHOD: The hippocampus of rats submitted to pilocarpine-induced long-lasting status epilepticus was analyzed to determine the expression of inflammatory molecules with RT-PCR and immunohistochemistry. RESULTS: Compared with controls, reduced levels of the kinin B2 receptors IL1β and TNFα were found in the hippocampus of rats submitted to long-lasting status epilepticus and treated with indomethacin. CONCLUSIONS: These data show that low doses of indomethacin could be employed to minimize inflammation during long-lasting status epilepticus.

Tityus serrulatus venom--A lethal cocktail.

Science.gov (United States)

Pucca, Manuela Berto; Cerni, Felipe Augusto; Pinheiro Junior, Ernesto Lopes; Bordon, Karla de Castro Figueiredo; Amorim, Fernanda Gobbi; Cordeiro, Francielle Almeida; Longhim, Heloisa Tavoni; Cremonez, Caroline Marroni; Oliveira, Guilherme Honda; Arantes, Eliane Candiani

2015-12-15

Tityus serrulatus (Ts) is the main scorpion species of medical importance in Brazil. Ts venom is composed of several compounds such as mucus, inorganic salts, lipids, amines, nucleotides, enzymes, kallikrein inhibitor, natriuretic peptide, proteins with high molecular mass, peptides, free amino acids and neurotoxins. Neurotoxins are considered the most responsible for the envenoming syndrome due to their pharmacological action on ion channels such as voltage-gated sodium (Nav) and potassium (Kv) channels. The major goal of this review is to present important advances in Ts envenoming research, correlating both the crude Ts venom and isolated toxins with alterations observed in all human systems. The most remarkable event lies in the Ts induced massive releasing of neurotransmitters influencing, directly or indirectly, the entire body. Ts venom proved to extremely affect nervous and muscular systems, to modulate the immune system, to induce cardiac disorders, to cause pulmonary edema, to decrease urinary flow and to alter endocrine, exocrine, reproductive, integumentary, skeletal and digestive functions. Therefore, Ts venom possesses toxins affecting all anatomic systems, making it a lethal cocktail. However, its low lethality may be due to the low venom mass injected, to the different venom compositions, the body characteristics and health conditions of the victim and the local of Ts sting. Furthermore, we also described the different treatments employed during envenoming cases. In particular, throughout the review, an effort will be made to provide information from an extensive documented studies concerning Ts venom in vitro, in animals and in humans (a total of 151 references). Copyright © 2015 Elsevier Ltd. All rights reserved.

Analysis of Milk from Mothers Who Delivered Prematurely Reveals Few Changes in Proteases and Protease Inhibitors across Gestational Age at Birth and Infant Postnatal Age.

Science.gov (United States)

Demers-Mathieu, Veronique; Nielsen, Søren Drud; Underwood, Mark A; Borghese, Robyn; Dallas, David C

2017-06-01

Background: Peptidomics research has demonstrated that protease activity is higher in breast milk from preterm-delivering mothers than from term-delivering mothers. However, to our knowledge, the effect of the degree of prematurity and postnatal age on proteases and protease inhibitors in human milk remains unknown. Objective: We aimed to determine the change of proteases and protease inhibitors in milk from mothers who delivered prematurely across gestational age (GA) and postnatal age. Methods: Milk samples were collected from 18 mothers aged 26-40 y who delivered preterm infants and who lacked mastitis. For analysis, samples were separated into 2 groups: 9 from early GA (EGA) (24-26 wk GA)-delivering mothers and 9 from late GA (LGA) (27-32 wk GA)-delivering mothers. Within the 9 samples in each group, the collection time ranged from postnatal days 2 to 47. The activity and predicted activity of proteases in preterm milk were determined with the use of fluorometric and spectrophotometric assays and peptidomics, respectively. Protease and protease inhibitor concentrations were determined with the use of ELISA. Linear mixed models were applied to compare enzymes across GA and postnatal age. Results: Carboxypeptidase B2, kallikrein, plasmin, elastase, thrombin, and cytosol aminopeptidase were present and active in the milk of preterm-delivering mothers. Most milk protease and antiprotease concentrations did not change with GA or postnatal age. However, the concentration and activity of kallikrein, the most abundant and active protease in preterm milk, increased by 25.4 ng · mL -1 · d -1 and 0.454 μg · mL -1 · d -1 postnatally, respectively, in EGA milk samples while remaining stable in LGA milk samples. Conclusions: This research demonstrates that proteases are active in human milk and begin to degrade milk protein within the mammary gland before consumption by infants. Proteases and protease inhibitors in milk from mothers of premature infants mostly did not

Bauhinia bauhinioides cruzipain inhibitor reduces endothelial proliferation and induces an increase of the intracellular Ca2+ concentration.

Science.gov (United States)

Bilgin, Mehmet; Neuhof, Christiane; Doerr, Oliver; Benscheid, Utz; Andrade, Sheila S; Most, Astrid; Abdallah, Yaser; Parahuleva, Mariana; Guenduez, Dursun; Oliva, Maria L; Erdogan, Ali

2010-12-01

Proteinase inhibitors, isolated from different types of Bauhinia, have an effect on apoptosis, angiogenesis and inflammation. The Bauhinia bauhinioides cruzipain inhibitor (BbCI) is a Kunitz-type inhibitor and inactivates the cysteine proteinases cruzipain and cruzain from Trypanosoma cruzi. Cruzipain and tissue kallikrein have similar biochemical properties, e.g. the proteolytic cleavage of the kininogen precursor of lys-bradykinin. Tissue kallikrein stimulation in endothelial cells causes migration and capillary tube formation. The aim of this study was to examine whether the antiproliferative effect of BbCI is dependent on changes of the intracellular calcium concentration and membrane hyperpolarization. Endothelial cells were isolated from human umbilical cord veins (HUVEC). For proliferation experiments, HUVEC were incubated with BbCI (10-100 μmol/L) for 48 h. The proliferation was detected by cell counting with a Neubauer chamber. The effect of BbCI (10-100 μM) on the membrane potential was measured with the fluorescence dye DiBAC4(3) and the effect on [Ca+2]i with the fluorescence probe Fluo-3 AM. The change of the fluorescence intensity was determined with a GENios plate reader (Tecan). The experiments showed that BbCI (10-100 μmol/L) reduces the endothelial cell proliferation significantly in a concentration-dependent manner with a maximum effect at 100 μmol/L (35.1±1.8% as compared to control (p≤0.05; n=45)). As compared to the control, the addition of BbCI (100 μmol/L) caused a significant increase of systolic Ca2+ of 28.4±5.0% after 30 min incubation. HUVEC treatment with BbCI (100 μmol/L) showed a weak but significant decrease of the membrane potential of 9.5±0.9% as compared to control (p≤0.05; n=80). BbCI influenced significantly the endothelial proliferation, the intracellular Ca2+ concentration and the membrane potential.

Urinary serine proteases and activation of ENaC in kidney

DEFF Research Database (Denmark)

Svenningsen, Per; Andersen, Henrik; Nielsen, Lise Hald

2015-01-01

with albuminuria compatible with impaired renal Na(+) excretion: hypertension and volume retention is secondary to proteinuria in, e.g., preeclampsia and nephrotic syndrome; plasma concentrations of renin, angiotensin II, and aldosterone are frequently suppressed in proteinuric conditions, e.g., preeclampsia......Serine proteases, both soluble and cell-attached, can activate the epithelial sodium channel (ENaC) proteolytically through release of a putative 43-mer inhibitory tract from the ectodomain of the γ-subunit. ENaC controls renal Na(+) excretion and loss-of-function mutations lead to low blood...... pressure, while gain-of-function mutations lead to impaired Na(+) excretion, hypertension, and hypokalemia. We review an emerging pathophysiological concept that aberrant glomerular filtration of plasma proteases, e.g., plasmin, prostasin, and kallikrein, contributes to proteolytic activation of ENaC, both...

Characterization of the gila monster (Heloderma suspectum suspectum) venom proteome

DEFF Research Database (Denmark)

Sanggaard, Kristian Wejse; Dyrlund, Thomas Franck; Thomsen, Line Rold

2015-01-01

of venom. Of these proteins, 19 have not previously been identified in helodermatid venom. The data showed that helodermatid venom is complex and that this complexity is caused by genetic isoforms and post-translational modifications including proteolytic processing. In addition, the venom proteome...... analysis revealed that the major constituents of the gila monster venom are kallikrein-like serine proteinases (EC 3.4.21) and phospholipase A2 (type III) enzymes (EC 3.1.1.4). A neuroendocrine convertase 1 homolog that most likely converts the proforms of the previously identified bioactive exendins...... into the mature and active forms was identified suggesting that these peptide toxins are secreted as proforms that are activated by proteolytic cleavage following secretion as opposed to being activated intracellularly. The presented global protein identification-analysis provides the first overview...

AYVALIDERE HAVZASINDA (SÜLEYMANPAŞA / TEKİRDAĞ JEOMORFOLOJİK FAKTÖRLERİN TOPRAK ÖZELLİKLERİ ÜZERİNE ETKİLERİ

Directory of Open Access Journals (Sweden)

Emre ÖZŞAHİN

2016-02-01

Full Text Available Bu çalışmada, jeomorfolojik faktörlerin toprak özellikleri üzerine etkileri Ayvalıdere Havzası örneğinde incelenmiştir. Bu etkilerin örnek bir havza dâhilinde incelenmesi çalışmanın önemini teşkil etmektedir. Çalışmada 1:25.000 ölçekli KIRKLARELİ F19-d4 ve BANDIRMA G19-a1 numa- ralı topoğrafya haritaları kullanılmıştır. Yöntem olarak ise öncelikle havza alanının jeomorfolojik özellikleri tespit edilmiştir. Ardından başka araştırmacılar tarafından yaptırılan toprak örneklerinin analizlerinden ve çalışma bulgularından istifade edilerek havzanın detaylı toprak haritası oluşturul- muştur. Gerek jeomorfolojik özellikler (yer şekilleri, eğim, bakı, yükselti gerekse toprak özellikleri CBS (Coğrafi Bilgi Sistemleri ortamında karşılaştırılarak, havzada toprakların dağılışında jeomor- folojik faktörlerin etkisi irdelenmiştir. Çalışma sonunda yer şekilleri ile toprak özellikleri arasındaki ilişkinin kısa mesafeler dâhilinde büyük değişiklikler sunduğunu belirlenmiş ve vurgulanmıştır. Bu ilişkinin daha detaylı çalışmalarla ortaya konması gereklidir. Böylece elde edilen sonuçlarla toprak kaynaklarının korunması, doğru kullanımı ve planlanması konusunda önemli adımlar atılabilir. Nihai olarak gerek jeomorfolojik gerekse pedolojik özellikleri konu alan benzer çalışmalarda toprak ve yer şekilleri arasındaki münasebetin araştırılması doğal ortamı daha iyi anlayıp, analiz etmemize yardımcı olacaktır.

Restoran İşletmelerinde Hizmet Hataları, Hizmet Telafi Stratejileri Ve Müşteri Memnuniyeti İlişkisi

OpenAIRE

ÇALIŞKAN, Osman

2013-01-01

Çalışmada geleneksel ve hızlı servis sunan restoranlarda ortaya çıkan hizmet hat alarının ve hizmet telafi stratejilerinin belirlenmesi ve hangi hizmet hatalarının hangi telafilerle karşılandığının tespit edilmesi amaçlanmaktadır. Bununla birlikte çalışmada restoran türüne göre (geleneksel veya hızlı servis sunan) restoranın yanıtı açısından farklılığın olup olmadığının ve hizmet telafisi ile müşteri memnuniyeti arasında bir ilişkinin olup olmadığının saptanması da amaçlanmaktadır. Araştırma,...

14-18 yaş arası ergenlerin benlik saygısı ve psikolojik dayanıklılık düzeyleri arasındaki ilişki

OpenAIRE

Sarıkaya, Açelya

2015-01-01

Bu araştırmanın amacı lise çağındaki ergenlerin benlik saygıları ile psikolojik dayanıklılıkları arasındaki ilişkinin incelenmesidir. Bunun yanı sıra teorik anlamda benlik saygısıyla ilişkili olduğu düşünülen; cinsiyet, yaş, doğum sırası, ebeveynlerin eğitim durumu, ebeveynlerin birliktelik durumu, algılanan sosyoekonomik düzey gibi demografik özelliklerin de bu değişkenle ilişkileri araştırılmıştır. Araştırmada ilişkisel tarama modeli kullanılmıştır ve araştırmanın evrenini Yalova ...

YÜKSEK-DÜŞÜK BAĞLAMLI İLETİŞİM İLE ÖRGÜTSEL MUHALEFET DAVRANIŞLARI ARASINDAKİ İLİŞKİ: AKADEMİSYENLER ÜZERİNE BİR ARAŞTIRMA -THE RELATIONSHIP BETWEEN HIGH-LOW CONTEXT COMMUNICATION AND ORGANIZATIONAL DISSENT BEHAVIORS: A RESEARCH ON SÜLEYMAN DEMİREL UNIVERSITY ACADEMIC STAFF

OpenAIRE

İZGÜDEN, Dilruba; ERDEM, Ramazan

2017-01-01

Buçalışmada, üniversitede çalışmakta olan akademik personelin örgütsel muhalefetdavranışlarının ve yüksek-düşük bağlamlı iletişim eğilimlerinin ölçülmesi ve aralarındakiilişkinin tespit edilmesi amaçlanmaktadır. Araştırmanın evrenini SüleymanDemirel Üniversitesi’ne bağlı fakültelerde çalışan akademik personel oluşturmaktadır.Araştırma kapsamında 201 akademik personele anket uygulanmıştır. Veri toplamaaracı olarak Erdem (2006) tarafından Hall’ın Yüksek Bağlam-Düşük Bağlam Modeliçerçevesinde ge...

TÜRKİYE’NİN AB’YE ÜYELİK SÜRECİNİN MALİ GÖSTERGELER AÇISINDAN AB’NİN YENİ ÜYE ÜLKELERİYLE KARŞILAŞTIRILMASI

OpenAIRE

YAVUZ, Hakan; YAVUZ, Sinem

2015-01-01

Türkiye’nin Avrupa Birliği (AB) ile ilişkisi uzun bir tarihsel geçmişe dayanmasına rağmen, halen nihai hedefine ulaşamamıştır. Ancak tam üyelik yolunda önemli adımların atıldığı söylenebilir. Söz konusu gelişmelere paralel olarak, Türkiye-AB ilişkilerine yönelik literatür de genişlemektedir. Literatürde bazı çalışmalar ilişkinin ekonomik, mali, bazı çalışmalar da siyasi, kültürel ve sosyal boyutunu ele almaktadır. Bu çalışmanın amacı, Türkiye’nin AB üyelik sürecinin mali göstergelere gösterdi...

A Multiplex Protein Panel Applied to Cerebrospinal Fluid Reveals Three New Biomarker Candidates in ALS but None in Neuropathic Pain Patients.

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Anne-Li Lind

Full Text Available The objective of this study was to develop and apply a novel multiplex panel of solid-phase proximity ligation assays (SP-PLA requiring only 20 μL of samples, as a tool for discovering protein biomarkers for neurological disease and treatment thereof in cerebrospinal fluid (CSF. We applied the SP-PLA to samples from two sets of patients with poorly understood nervous system pathologies amyotrophic lateral sclerosis (ALS and neuropathic pain, where patients were treated with spinal cord stimulation (SCS. Forty-seven inflammatory and neurotrophic proteins were measured in samples from 20 ALS patients and 15 neuropathic pain patients, and compared to normal concentrations in CSF from control individuals. Nineteen of the 47 proteins were detectable in more than 95% of the 72 controls. None of the 21 proteins detectable in CSF from neuropathic pain patients were significantly altered by SCS. The levels of the three proteins, follistatin, interleukin-1 alpha, and kallikrein-5 were all significantly reduced in the ALS group compared to age-matched controls. These results demonstrate the utility of purpose designed multiplex SP-PLA panels in CSF biomarker research for understanding neuropathological and neurotherapeutic mechanisms. The protein changes found in the CSF of ALS patients may be of diagnostic interest.

Effects of oversulfated and fucosylated chondroitin sulfates on coagulation. Challenges for the study of anticoagulant polysaccharides.

Science.gov (United States)

Fonseca, Roberto J C; Oliveira, Stephan-Nicollas M C G; Pomin, Vitor H; Mecawi, André S; Araujo, Iracema G; Mourão, Paulo A S

2010-05-01

We report the effects of a chemically oversulfated chondroitin sulfate and a naturally fucosylated chondroitin sulfate on the coagulation system. The former has been recently identified as a contaminant of heparin preparations and the latter has been proposed as an alternative anticoagulant. The mechanism of action of these polymers on coagulation is complex and target different components of the coagulation system. They have serpin-independent anticoagulant activity, which preponderates in plasma. They also have serpin-dependent anticoagulant activity but differ significantly in the target coagulation protease and preferential serpin. Their anticoagulant effects differ even more markedly when tested as inhibitors of coagulation proteases using plasma as a source of serpins. It is possible that the difference is due to the high availability of fucosylated chondroitin sulfate whereas oversulfated chondroitin sulfate has strong unspecific binding to plasma protein and low availability for the binding to serpins. When tested using a venous thrombosis experimental model, oversulfated chondroitin sulfate is less potent as an antithrombotic agent than fucosylated chondroitin sulfate. These highly sulfated chondroitin sulfates activate factor XII in in vitro assays, based on kallikrein release. However, only fucosylated chondroitin sulfate induces hypotension when intravenously injected into rats. In conclusion, the complexity of the regulatory mechanisms involved in the action of highly sulfated polysaccharides in coagulation requires their analysis by a combination of in vitro and in vivo assays. Our results are relevant due to the urgent need for new anticoagulant drugs or alternative sources of heparin.

Two new bradykinin-related peptides from the venom of the social wasp Protopolybia exigua (Saussure).

Science.gov (United States)

Mendes, Maria Anita; Palma, Mario Sergio

2006-11-01

Two bradykinin-related peptides (Protopolybiakinin-I and Protopolybiakinin-II) were isolated from the venom of the social wasp Protopolybia exigua by RP-HPLC, and sequenced by Edman degradation method. Peptide sequences of Protopolybiakinin-I and Protopolybiakinin-II were DKNKKPIRVGGRRPPGFTR-OH and DKNKKPIWMAGFPGFTPIR-OH, respectively. Synthetic peptides with identical sequences to the bradykinin-related peptides and their biological functions were characterized. Protopolybiakinin-I caused less potent constriction of the isolated rat ileum muscles than bradykinin (BK). In addition, it caused degranulation of mast cells which was seven times more potent than BK. This peptide causes algesic effects due to the direct activation of B(2)-receptors. Protopolybiakinin-II is not an agonist of rat ileum muscle and had no algesic effects. However, Protopolybiakinin-II was found to be 10 times more potent as a mast cell degranulator than BK. The amino acid sequence of Protopolybiakinin-I is the longest among the known wasp kinins.

Physiological and biochemical aspects of the effect of ionizing radiations on the lung parenchyma

International Nuclear Information System (INIS)

Pasquier, Christian.

1975-03-01

Concerning the biochemical reactions of the lung parenchyma to irradiation the following points have been developed. Role of biochemically active substances (histamine, serotonin, kinins, catecholamines, prostaglandins) in the early reaction of the lung to irradiation, their common feature being their vascular impact point. Lung irradiation and lipids (fatty acids and lipid metabolism in general); irradiation, by raising the proportion of unsaturated at the expense of saturated fatty acids, may give rise to serious physiological respiratory disorders. Lung irradiation and blood fluidity (fibrinolytic activity, heparin, platelet factors). Pulmonary interstitium and irradiation (of the three interstitium components collagen plays a preferential part). Irradiation and immunological lung reaction (reasons behind the immunological theory, immunological assistance, immunological mechanism of pulmonary reactions towards pollutants). Enzymatic lung radiolesion indicators. Three kinds of physiological changes have been considered. Vascular physiology disturbances caused by the initial biochemical reactions; anomalies of physiological or functional trials, images of the lesion formed; disorders of the cell physiology of carcinogenesis [fr

BEŞ FAKTÖR KİŞİLİK MODELİ VE ÖRGÜTSEL MUHALEFET ARASINDAKİ İLİŞKİ ÜZERİNE BİR ARAŞTIRMA

OpenAIRE

ÖTKEN, Ayşe Begüm; CENKCİ, Tuna

2013-01-01

BEŞ FAKTÖR KİŞİLİK MODELİ VE ÖRGÜTSEL MUHALEFET ARASINDAKİ İLİŞKİ ÜZERİNE BİR ARAŞTIRMAÖzet: Örgüt içerisindeki ya da örgüt ile ilgili anlaşmazlıkların ve karşıt fikirlerin sözlü ifadesi [1] olarak tanımlanan örgütsel muhalefet, daha çok bireysel bir davranış olarak görülmektedir. Bu nedenledir ki, özellikle, kişilik özellikleri ile muhalefet arasındaki ilişkinin araştırılması konuya önemli bakış açısı sağlamaktadır. Bu çalışmanın amacı örgütsel muhalefete bireysel açıdan yaklaşmak ve beş fak...

Angiotensin and bradykinin interactions with phospholipids

International Nuclear Information System (INIS)

Elliott, M.E.; Goodfriend, T.L.

1979-01-01

Reversible interactions were demonstrated between some phospholipids and some polypeptides related to angiotensin and bradykinin. The extent of the interaction was dependent on the structures of the lipid and peptide. The naturally occurring compounds that interacted most avidly were cardiolipin and (des-Asp 1 )-angiotensins. The apparent dissociation constant of this complex in chloroform was 10 -5 M. The complex contained more than one cardiolipin molecule/molecule of peptide. Kinins interacted most strongly with lecithin. The phospholipids altered the chromatographic behaviour of radioiodinated derivatives of the polypeptides, and solubilized radioactive and unlabeled polypeptides in chloroform. In aqueous media, cardiolipin suspensions preferentially bound (des-Asp 1 )-angiotensin II, and inhibited its binding by antibody. The interactions were sensitive to pH and cations in the aqueous phase, and were reversed by some reagents added to the organic phase. These interactions have direct implications for binding reactions of peptides in vitro, and may bear upon the actions of the hormones in vivo. (Auth.)

Biostable Agonists that Match or Exceed Activity of Native Insect Kinins on Recombinant Arthropod GPCRs

Science.gov (United States)

2009-01-01

Drosophila melanogaster and the honey bee Apis mellifera. Prog. Neurobiol. 80, 1–19. Holman, G.M., Nachman, R.J., Wright, M.S., 1990. Insect...Introduction G- Protein -coupled receptors (GPCRs) are seven transmembrane cell surface proteins that are activated by diverse stimuli such as biogenic amines...neuropeptides and protein hormones. A distinct intracellular response, mostly through their heterotrimeric G-pro- tein, is initiated when GPCRs are

iTRAQ based investigation of plasma proteins in HIV infected and HIV/HBV coinfected patients - C9 and KLK are related to HIV/HBV coinfection.

Science.gov (United States)

Sun, Tao; Liu, Li; Wu, Ao; Zhang, Yujiao; Jia, Xiaofang; Yin, Lin; Lu, Hongzhou; Zhang, Lijun

2017-10-01

Human immunodeficiency virus (HIV) and hepatitis B virus (HBV) share similar routes of transmission, and rapid progression of hepatic and immunodeficiency diseases has been observed in coinfected individuals. Our main objective was to investigate the molecular mechanism of HIV/HBV coinfections. We selected HIV infected and HIV/HBV coinfected patients with and without Highly Active Antiretroviral Therapy (HAART). Low abundance proteins enriched using a multiple affinity removal system (MARS) were labeled with isobaric tags for relative and absolute quantitation (iTRAQ) kits and analyzed using liquid chromatography-mass spectrometry (LC-MS). The differential proteins were analyzed by Gene Ontology (GO) database. A total of 41 differential proteins were found in HIV/HBV coinfected patients as compared to HIV mono-infected patients with or without HAART treatment, including 7 common HBV-regulated proteins. The proteins involved in complement and coagulation pathways were significantly enriched, including plasma kallikrein (KLK) and complement component C9 (C9). C9 and KLK were verified to be down-regulated in HIV/HBV coinfected patients through ELISA analysis. The present iTRAQ based proteomic analyses identified 7 proteins that are related to HIV/HBV coinfection. HBV might influence hepatic and immune functions by deregulating complement and coagulation pathways. C9 and KLK could potentially be used as targets for the treatment of HIV/HBV coinfections. Copyright © 2017. Published by Elsevier Ltd.

Developing a Novel Therapeutic Strategy Targeting Kallikrein-4 to Inhibit Prostate Cancer Growth and Metastasis

Science.gov (United States)

2015-08-01

Medical Center, USA) were maintained in RPMI media containing 5% fetal bovine serum (Gibco, Life Technologies). All cell lines were incubated at 37°C in... acidosis upon degradation.35–38 Thus, a theranostic device that enters a tumour cell via receptor mediated endo- cytosis can undergo rapid degradation of...Technologies, Mulgrave, Vic, Aust) containing 10% fetal bovine serum (FBS; Moregate, Brisbane, Aust). The targeted and non- targeted polymers were made to 5

Hypercoagulability and the risk of myocardial infarction and ischemic stroke in young women.

Science.gov (United States)

Siegerink, B; Maino, A; Algra, A; Rosendaal, F R

2015-09-01

Myocardial infarction (MI) and ischemic stroke (IS) are acute forms of arterial thrombosis and share some, but not all, risk factors, indicating different pathophysiological mechanisms. This study aims to determine if hypercoagulability has a differential effect on the risk of MI and IS. We reviewed the results from the Risk of Arterial Thrombosis in Relation to Oral Contraceptives study, a population-based case-control study involving young women ( 1; for 12 (41%), it was > 2; and for 5 (17%), it was > 2.75. The five risk factors with the largest differences in associations were high levels of activated factor XI (FXI) and FXII, kallikrein, the presence of lupus anticoagulans, and a genetic variation in the FXIII gene. In young women, prothrombotic factors are associated more with the risk of IS than with MI risk, suggesting a different role of hypercoagulability in the mechanism leading to these two diseases. © 2015 International Society on Thrombosis and Haemostasis.

γ-irradiation-induced mortality: protective effect of protease inhibitors in chickens and mice

International Nuclear Information System (INIS)

Palladino, M.A.; Galton, J.E.; Troll, W.; Thorbecke, G.J.

1982-01-01

Chickens (Gallus domesticus) were protected from the acute γ-irradiation-induced mortality (within 24 hours) by the proteolytic enzyme inhibitors, soy-bean trypsin inhibitor (SBTI), lima bean inhibitor (LBTI), antipain, α-N-benzoyl-L-arginine ethyl ester HCl (BAEE), trasylol, and leupeptin. Several other enzyme inhibitors, p-tosyl-L-arginine methyl ester HCl (TAME), α-tosyl-lysyl-chloromethyl ketone HCl (TLCK) and epsilon-amino caproic acid (EACA), did not protect. EACA even increased the mortality caused by γ-irradiation. The pattern of protective enzyme inhibitors suggests involvement of a kallikrein-like enzyme. SBTI and antipain also protected against low range lethal γ-irradiation exposures, 690 R in BALB/c and 880 R in SJL/J mice. It is suggested that enhanced vascular permeability, which in chickens is known to be the cause of the irradiation mortality during the first 24 hours, may also contribute to the mortality in mice during the first week after irradiation. (author)

Other biomarkers for detecting prostate cancer.

Science.gov (United States)

Nogueira, Lucas; Corradi, Renato; Eastham, James A

2010-01-01

Prostate-specific antigen (PSA) has been used for detecting prostate cancer since 1994. Although it is the best cancer biomarker available, PSA is not perfect. It lacks both the sensitivity and specificity to accurately detect the presence of prostate cancer. None of the PSA thresholds currently in use consistently identify patients with prostate cancer and exclude patients without cancer. Novel approaches to improve our ability to detect prostate cancer and predict the course of the disease are needed. Additional methods for detecting prostate cancer have been evaluated. Despite the discovery of many new biomarkers, only a few have shown some clinical value. These markers include human kallikrein 2, urokinase-type plasminogen activator receptor, prostate-specific membrane antigen, early prostate cancer antigen, PCA3, alpha-methylacyl-CoA racemase and glutathione S-transferase pi hypermethylation. We review the reports on biomarkers for prostate cancer detection, and their possible role in the clinical practice.

Learning from eponyms: George F. Odland and Odland bodies

Directory of Open Access Journals (Sweden)

Rajiv Joshi

2014-01-01

Full Text Available Odland bodies (lamellar bodies are small sub-cellular structures of size 200-300 nm that are present in the upper spinous and granular cell layers of the epidermis. These act as processing and repository areas for lipids that contribute to the epidermal permeability barrier. They also contain proteases, cathepsin D, kallikrein and other proteins including corneo-desmosins. Recent information also credits them with a role in the local innate immune response as they contain beta 2 defensins, which are anti-microbial peptides with potent activity against Gram-negative bacteria and candida. Odland bodies are important for maintaining homeostasis of the epidermis and are involved in epidermal permeability barrier function, desquamation of keratinocytes, formation of the cornified envelope and in local anti-microbial immunity. This article reviews the structure and functions of these bodies with a brief biography of George F. Odland who first described these bodies in 1960 and whose name is eponymically associated with them.

FİNANSAL VEKTÖREL ZAMAN DİZİLERİNDE ÖZDEĞER-ÖZVEKTÖR ANALİZİYLE EŞZAMANLI VE GECİKMELİ DOĞRUSAL İLİŞKİLERİN TESBİTİ

Directory of Open Access Journals (Sweden)

REŞAT KASAP

2013-05-01

Full Text Available Bu çalışmada, vektörel zaman dizilerinde modelleme aşamasında, dizilerin birbirleriyle ilişkilerini ortaya koyan eşzamanlı ve gecikmeli doğrusal ilişkilerin tesbiti, iki farklı gerçek veri grubu üzerinde gösterilmiştir. Bunlardan birincisi, üç diziden oluşan Ziraat Bankası(TCZB’nın verdiği kredi dizileridir. Diğeri ise, ABD Doları’nın BP(İngiliz Sterlini, DM(Alman Markı, SF(İsviçre Frangı, ve YEN(Japon Yeni’e göre değişimlerini veren dört dizidir. Analizler sonucunda vektör AR(1 ile modellenen her iki grupdan; birincisinde doğrusal ilişkilerin her ikisinin de olmadığı, diğer veri grubunda ise her iki ilişkinin de var olduğu görülmüştür.

Induction of selective blood-tumor barrier permeability and macromolecular transport by a biostable kinin B1 receptor agonist in a glioma rat model.

Science.gov (United States)

Côté, Jérôme; Bovenzi, Veronica; Savard, Martin; Dubuc, Céléna; Fortier, Audrey; Neugebauer, Witold; Tremblay, Luc; Müller-Esterl, Werner; Tsanaclis, Ana-Maria; Lepage, Martin; Fortin, David; Gobeil, Fernand

2012-01-01

Treatment of malignant glioma with chemotherapy is limited mostly because of delivery impediment related to the blood-brain tumor barrier (BTB). B1 receptors (B1R), inducible prototypical G-protein coupled receptors (GPCR) can regulate permeability of vessels including possibly that of brain tumors. Here, we determine the extent of BTB permeability induced by the natural and synthetic peptide B1R agonists, LysdesArg(9)BK (LDBK) and SarLys[dPhe(8)]desArg(9)BK (NG29), in syngeneic F98 glioma-implanted Fischer rats. Ten days after tumor inoculation, we detected the presence of B1R on tumor cells and associated vasculature. NG29 infusion increased brain distribution volume and uptake profiles of paramagnetic probes (Magnevist and Gadomer) at tumoral sites (T(1)-weighted imaging). These effects were blocked by B1R antagonist and non-selective cyclooxygenase inhibitors, but not by B2R antagonist and non-selective nitric oxide synthase inhibitors. Consistent with MRI data, systemic co-administration of NG29 improved brain tumor delivery of Carboplatin chemotherapy (ICP-Mass spectrometry). We also detected elevated B1R expression in clinical samples of high-grade glioma. Our results documented a novel GPCR-signaling mechanism for promoting transient BTB disruption, involving activation of B1R and ensuing production of COX metabolites. They also underlined the potential value of synthetic biostable B1R agonists as selective BTB modulators for local delivery of different sized-therapeutics at (peri)tumoral sites.

Crystallization and preliminary X-ray analysis of a novel Kunitz-type kallikrein inhibitor from Bauhinia bauhinioides

Science.gov (United States)

Navarro, Marcos Vicente de A. S.; Vierira, Débora F.; Nagem, Ronaldo A. P.; de Araújo, Ana Paula U.; Oliva, Maria Luiza V.; Garratt, Richard C.

2005-01-01

A Kunitz-type protease inhibitor (BbKI) found in Bauhinia bauhinioides seeds has been overexpressed in Escherichia coli and crystallized at 293 K using PEG 4000 as the precipitant. X-ray diffraction data have been collected to 1.87 Å resolution using an in-house X-ray generator. The crystals of the recombinant protein (rBbKI) belong to the orthorhombic space group P212121, with unit-cell parameters a = 46.70, b = 64.14, c = 59.24 Å. Calculation of the Matthews coefficient suggests the presence of one monomer of rBbKI in the asymmetric unit, with a corresponding solvent content of 51% (V M = 2.5 Å3 Da−1). Iodinated crystals were prepared and a derivative data set was also collected at 2.1 Å resolution. Crystals soaked for a few seconds in a cryogenic solution containing 0.5 M NaI were found to be reasonably isomorphous to the native crystals. Furthermore, the presence of iodide anions could be confirmed in the NaI-derivatized crystal. Data sets from native and derivative crystals are being evaluated for use in crystal structure determination by means of the SIRAS (single isomorphous replacement with anomalous scattering) method. PMID:16511193

Crystallization and preliminary X-ray analysis of a novel Kunitz-type kallikrein inhibitor from Bauhinia bauhinioides

Energy Technology Data Exchange (ETDEWEB)

Navarro, Marcos Vicente de A. S.; Vierira, Débora F. [Institute of Physics of São Carlos, University of São Paulo, Avenida Trabalhador Sãocarlense 400, CEP 13560-970, São Carlos, SP (Brazil); Nagem, Ronaldo A. P. [Biochemistry and Immunology Department, Institute of Biological Sciences, Federal University of Minas Gerais, Avenida Antônio Carlos 6627, Caixa Postal 486, CEP 31270-901, Belo Horizonte, MG (Brazil); Araújo, Ana Paula U. de [Institute of Physics of São Carlos, University of São Paulo, Avenida Trabalhador Sãocarlense 400, CEP 13560-970, São Carlos, SP (Brazil); Oliva, Maria Luiza V. [Universidade Federal de São Paulo, Escola Paulista de Medicina, Rua Três de Maio 100, CEP 04044-020, São Paulo, SP (Brazil); Garratt, Richard C., E-mail: richard@if.sc.usp.br [Institute of Physics of São Carlos, University of São Paulo, Avenida Trabalhador Sãocarlense 400, CEP 13560-970, São Carlos, SP (Brazil)

2005-10-01

Crystallization and preliminary X-ray diffraction studies are reported for a novel Kunitz-type protease inhibitor from B. bauhinioides which contains no disulfide bridges. A Kunitz-type protease inhibitor (BbKI) found in Bauhinia bauhinioides seeds has been overexpressed in Escherichia coli and crystallized at 293 K using PEG 4000 as the precipitant. X-ray diffraction data have been collected to 1.87 Å resolution using an in-house X-ray generator. The crystals of the recombinant protein (rBbKI) belong to the orthorhombic space group P2{sub 1}2{sub 1}2{sub 1}, with unit-cell parameters a = 46.70, b = 64.14, c = 59.24 Å. Calculation of the Matthews coefficient suggests the presence of one monomer of rBbKI in the asymmetric unit, with a corresponding solvent content of 51% (V{sub M} = 2.5 Å{sup 3} Da{sup −1}). Iodinated crystals were prepared and a derivative data set was also collected at 2.1 Å resolution. Crystals soaked for a few seconds in a cryogenic solution containing 0.5 M NaI were found to be reasonably isomorphous to the native crystals. Furthermore, the presence of iodide anions could be confirmed in the NaI-derivatized crystal. Data sets from native and derivative crystals are being evaluated for use in crystal structure determination by means of the SIRAS (single isomorphous replacement with anomalous scattering) method.

Crystallization and preliminary X-ray analysis of a novel Kunitz-type kallikrein inhibitor from Bauhinia bauhinioides

International Nuclear Information System (INIS)

Navarro, Marcos Vicente de A. S.; Vierira, Débora F.; Nagem, Ronaldo A. P.; Araújo, Ana Paula U. de; Oliva, Maria Luiza V.; Garratt, Richard C.

2005-01-01

Crystallization and preliminary X-ray diffraction studies are reported for a novel Kunitz-type protease inhibitor from B. bauhinioides which contains no disulfide bridges. A Kunitz-type protease inhibitor (BbKI) found in Bauhinia bauhinioides seeds has been overexpressed in Escherichia coli and crystallized at 293 K using PEG 4000 as the precipitant. X-ray diffraction data have been collected to 1.87 Å resolution using an in-house X-ray generator. The crystals of the recombinant protein (rBbKI) belong to the orthorhombic space group P2 1 2 1 2 1 , with unit-cell parameters a = 46.70, b = 64.14, c = 59.24 Å. Calculation of the Matthews coefficient suggests the presence of one monomer of rBbKI in the asymmetric unit, with a corresponding solvent content of 51% (V M = 2.5 Å 3 Da −1 ). Iodinated crystals were prepared and a derivative data set was also collected at 2.1 Å resolution. Crystals soaked for a few seconds in a cryogenic solution containing 0.5 M NaI were found to be reasonably isomorphous to the native crystals. Furthermore, the presence of iodide anions could be confirmed in the NaI-derivatized crystal. Data sets from native and derivative crystals are being evaluated for use in crystal structure determination by means of the SIRAS (single isomorphous replacement with anomalous scattering) method

Induction of selective blood-tumor barrier permeability and macromolecular transport by a biostable kinin B1 receptor agonist in a glioma rat model.

Directory of Open Access Journals (Sweden)

Jérôme Côté

Full Text Available Treatment of malignant glioma with chemotherapy is limited mostly because of delivery impediment related to the blood-brain tumor barrier (BTB. B1 receptors (B1R, inducible prototypical G-protein coupled receptors (GPCR can regulate permeability of vessels including possibly that of brain tumors. Here, we determine the extent of BTB permeability induced by the natural and synthetic peptide B1R agonists, LysdesArg(9BK (LDBK and SarLys[dPhe(8]desArg(9BK (NG29, in syngeneic F98 glioma-implanted Fischer rats. Ten days after tumor inoculation, we detected the presence of B1R on tumor cells and associated vasculature. NG29 infusion increased brain distribution volume and uptake profiles of paramagnetic probes (Magnevist and Gadomer at tumoral sites (T(1-weighted imaging. These effects were blocked by B1R antagonist and non-selective cyclooxygenase inhibitors, but not by B2R antagonist and non-selective nitric oxide synthase inhibitors. Consistent with MRI data, systemic co-administration of NG29 improved brain tumor delivery of Carboplatin chemotherapy (ICP-Mass spectrometry. We also detected elevated B1R expression in clinical samples of high-grade glioma. Our results documented a novel GPCR-signaling mechanism for promoting transient BTB disruption, involving activation of B1R and ensuing production of COX metabolites. They also underlined the potential value of synthetic biostable B1R agonists as selective BTB modulators for local delivery of different sized-therapeutics at (peritumoral sites.

A secretome analysis reveals that PPARα is upregulated by fractionated-dose γ-irradiation in three-dimensional keratinocyte cultures

International Nuclear Information System (INIS)

Lee, Jee Yong; Kim, Hyun Ji; Yi, Jae Youn

2016-01-01

A three-dimensional (3D) environment composed of properly interconnected and differentiated cells that allows communication and cooperation among cells via secreted molecules would be expected to more accurately reflect cellular responses. Here, we investigated γ-irradiation-induced changes in the secretome of 3D-cultured keratinocytes. An analysis of keratinocyte secretome profiles following fractionated-dose γ-irradiation revealed changes in genes involved in cell adhesion, angiogenesis, and the immune system. Notably, peroxisome proliferator-activated receptor-(PPARα) was upregulated in response to fractionated-dose γ-irradiation. This upregulation was associated with an increase in the transcription of known PPARα target genes, including angiopoietin-like protein 4, dermokine and kallikrein-related peptide 12, which were differentially regulated by fractionated-dose γ-irradiation. Collectively, our data imply a mechanism linking γ-irradiation and secretome changes, and suggest that these changes could play a significant role in the coordinated cellular responses to harmful ionizing radiation, such as those associated with radiation therapy. This extension of our understanding of γ-irradiation-induced secretome changes has the potential to improve radiation therapy strategies. Control of inflammatory waves, improved wound healing, and stabilization of the skin barrier are imperative for minimizing such injuries. Therefore, PPARα agonists and antagonists have the potential to become important therapeutic agents for the treatment of γ-irradiation induced skin damage. Specifically, our analysis suggests that the undesirable consequences of long-term exposure to ionizing radiation could be alleviated by PPARα agonists

A secretome analysis reveals that PPARα is upregulated by fractionated-dose γ-irradiation in three-dimensional keratinocyte cultures

Energy Technology Data Exchange (ETDEWEB)

Lee, Jee Yong; Kim, Hyun Ji; Yi, Jae Youn [Korea Institute of Radiation and Medical Sciences, Daejeon (Korea, Republic of)

2016-05-15

A three-dimensional (3D) environment composed of properly interconnected and differentiated cells that allows communication and cooperation among cells via secreted molecules would be expected to more accurately reflect cellular responses. Here, we investigated γ-irradiation-induced changes in the secretome of 3D-cultured keratinocytes. An analysis of keratinocyte secretome profiles following fractionated-dose γ-irradiation revealed changes in genes involved in cell adhesion, angiogenesis, and the immune system. Notably, peroxisome proliferator-activated receptor-(PPARα) was upregulated in response to fractionated-dose γ-irradiation. This upregulation was associated with an increase in the transcription of known PPARα target genes, including angiopoietin-like protein 4, dermokine and kallikrein-related peptide 12, which were differentially regulated by fractionated-dose γ-irradiation. Collectively, our data imply a mechanism linking γ-irradiation and secretome changes, and suggest that these changes could play a significant role in the coordinated cellular responses to harmful ionizing radiation, such as those associated with radiation therapy. This extension of our understanding of γ-irradiation-induced secretome changes has the potential to improve radiation therapy strategies. Control of inflammatory waves, improved wound healing, and stabilization of the skin barrier are imperative for minimizing such injuries. Therefore, PPARα agonists and antagonists have the potential to become important therapeutic agents for the treatment of γ-irradiation induced skin damage. Specifically, our analysis suggests that the undesirable consequences of long-term exposure to ionizing radiation could be alleviated by PPARα agonists.

Paracrine control of vascularization and neurogenesis by neurotrophins.

Science.gov (United States)

Emanueli, Costanza; Schratzberger, Peter; Kirchmair, Rudolf; Madeddu, Paolo

2003-10-01

The neuronal system plays a fundamental role in the maturation of primitive embryonic vascular network by providing a paracrine template for blood vessel branching and arterial differentiation. Furthermore, postnatal vascular and neural regeneration cooperate in the healing of damaged tissue. Neurogenesis continues in adulthood although confined to specific brain regions. Following ischaemic insult, neural staminal cells contribute towards the healing process through the stimulation of neurogenesis and vasculogenesis. Evidence indicates that nerves and blood vessels exert a reciprocal control of their own growth by paracrine mechanisms. For instance, guidance factors, including vascular endothelial growth factor A (VEGF-A) and semaphorins, which share the ability of binding neuropilin receptors, play a pivotal role in the tridimensional growth pattern of arterial vessels and nerves. Animal models and clinical studies have demonstrated a role of VEGF-A in the pathogenesis of ischaemic and diabetic neuropathies. Further, supplementation with VEGF-A ameliorates neuronal recovery by exerting protective effects on nerves and stimulating reparative neovascularization. Human tissue kallikrein, a recently discovered angiogenic and arteriogenic factor, accelerates neuronal recovery by stimulating the growth of vasa nervorum. Conversely, the neurotrophin nerve growth factor, known to regulate neuronal survival and differentiation, is now regarded as a stimulator of angiogenesis and arteriogenesis. These results indicate that angiogenesis and neurogenesis are paracrinally regulated by growth factors released by endothelial cells and neurons. Supplementation of these growth factors, alone or in combination, could benefit the treatment of ischaemic diseases and neuropathies.

De werking van de hydro- en acetylverbindingen van kinidine en kinine op het hart van Rana esculenta

NARCIS (Netherlands)

Sibie, Johan Dirk

1942-01-01

In hoofdstuk I werd een inleiding gegeven betreffende de geschiedenis van de kina en van het begin der kinacultuur op Java, de chemie der kinaälkaloïden en enkele aspecten der pharmacologische werking van de kinaderivaten. ... Zie: Samenvatting

Pervasive Adaptive Evolution in Primate Seminal Proteins.

Directory of Open Access Journals (Sweden)

2005-09-01

Full Text Available Seminal fluid proteins show striking effects on reproduction, involving manipulation of female behavior and physiology, mechanisms of sperm competition, and pathogen defense. Strong adaptive pressures are expected for such manifestations of sexual selection and host defense, but the extent of positive selection in seminal fluid proteins from divergent taxa is unknown. We identified adaptive evolution in primate seminal proteins using genomic resources in a tissue-specific study. We found extensive signatures of positive selection when comparing 161 human seminal fluid proteins and 2,858 prostate-expressed genes to those in chimpanzee. Seven of eight outstanding genes yielded statistically significant evidence of positive selection when analyzed in divergent primates. Functional clues were gained through divergent analysis, including several cases of species-specific loss of function in copulatory plug genes, and statistically significant spatial clustering of positively selected sites near the active site of kallikrein 2. This study reveals previously unidentified positive selection in seven primate seminal proteins, and when considered with findings in Drosophila, indicates that extensive positive selection is found in seminal fluid across divergent taxonomic groups.

Risk factors for the development of essential hypertension in a Mongolian population of China: a case-control study.

Science.gov (United States)

Dalai, N; Cui, H; Yan, M; Rile, G; Li, S; Su, X

2014-04-29

Lifestyle, habits, diet, and genetics are all important factors associated with the prevalence of hypertension. Many association studies have been performed in the Chinese Han population, whereas data explaining the high prevalence of hypertension in the Mongolian population remain scarce. In the present study, we aimed to determine the factors associated with the development of essential hypertension in Mongolians. A total of 194 hypertensive cases and 201 controls from Dongwu County were enrolled in the study. Demographics, anthropometric and blood biochemical parameters, food intake, lifestyle, habits, education, occupation, and family history were recorded for each subject. Genotype and allele frequencies of six single nucleotide polymorphisms (SNPs) of the kallikrein 1 (KLK1) gene were also examined. Mean body mass index, waistline, hipline, blood sugar, blood urea nitrogen, creatinine, uric acid, total cholesterol, triglyceride, and low-density lipoprotein levels were all significantly higher in the hypertensive group (Pcontrols (Pcontrol groups (P>0.05). These results suggest that dietary history and habits have the most important influence on the development of essential hypertension in the Mongolian population.

Üniversite öğrencilerinde ebeveyn kabulü ile psikolojik uyum arasındaki ilişkinin incelenmesi

OpenAIRE

KAVAK, Güler

2013-01-01

Bu çalışmada, alanyazında yer alan anne-baba kabul/reddi vepsikolojik uyum değişkenleri arasındaki ilişkilerin, kuramsal tartışmalar ve varolan araştırmalar ışığında bir yapısal model bağlamında test edilmesiamaçlanmıştır. Çalışmada ayrıca, anne-baba kabul/reddi ile psikolojik uyumdeğişkenlerinin cinsiyet ve anne-baba eğitim durumuna göre değişipdeğişmediği de incelenmiştir. Bunlara ek olarak, katılımcıların annelerinden vebabalarından algıladıkları kabul/reddin psikolojik uyumu yord...

Affinity and specificity of serine endopeptidase-protein inhibitor interactions. Empirical free energy calculations based on X-ray crystallographic structures.

Science.gov (United States)

Krystek, S; Stouch, T; Novotny, J

1993-12-05

An empirical function was used to calculate free energy change (delta G) of complex formation between the following inhibitors and enzymes: Kunitz inhibitor (BPTI) with trypsin, trypsinogen and kallikrein; turkey ovomucoid 3rd domain (OMTKY3) with alpha-chymotrypsin and the Streptomyces griseus protease B; the potato chymotrypsin inhibitor with the protease B; and the barely chymotrypsin inhibitor and eglin-c with subtilisin and thermitase. Using X-ray coordinates of the nine complexes, we estimated the contributions that hydrophobic effect, electrostatic interactions and side-chain conformational entropy make towards the stability of the complexes. The calculated delta G values showed good agreement with the experimentally measured ones, the only exception being the kallikrein/BPTI complex whose X-ray structure was solved at an exceptionally low pH. In complexes with different enzymes, the same inhibitor residues contributed identically towards complex formation (delta G(residue) Spearman rank correlation coefficient 0.7 to 1.0). The most productive enzyme-contacting residues in OMTKY3, eglin-c, and the chymotrypsin inhibitors were found in analogous positions on their respective binding loops; thus, our calculations identified a functional (energetic) motif that parallels the well-known structural similarity of the binding loops. The delta G values calculated for BPTI complexed with trypsin (-21.7 kcal) and trypsinogen (-23.4 kcal) were similar and close to the experimental delta G value of the trypsin/BPTI complex (-18.1 kcal), lending support to the suggestion that the 10(7) difference in the observed stabilities (KA) of these two complexes reflects the energetic cost of conformational changes induced in trypsinogen during the pre-equilibrium stages of complex formation. In almost all of the complexes studied, the stabilization free energy contributed by the inhibitors was larger than that donated by the enzymes. In the trypsin-BPTI complex, the calculated

Serine protease isoforms in Gloydius intermedius venom: Full sequences, molecular phylogeny and evolutionary implications.

Science.gov (United States)

Yang, Zhang-Min; Yu, Hui; Liu, Zhen-Zhen; Pei, Jian-Zhu; Yang, Yu-E; Yan, Su-Xian; Zhang, Cui; Zhao, Wen-Long; Wang, Zhe-Zhi; Wang, Ying-Ming; Tsai, Inn-Ho

2017-07-05

Nine distinct venom serine proteases (vSPs) of Gloydius intermedius were studied by transcriptomic, sub-proteomic and phylogenetic analyses. Their complete amino acid sequences were deduced after Expression Sequence Tag (EST) analyses followed by cDNA cloning and sequencing. These vSPs appear to be paralogs and contain the catalytic triads and 1-4 potential N-glycosylation sites. Their relative expression levels evaluated by qPCR were grossly consistent with their EST hit-numbers. The major vSPs were purified by HPLC and their N-terminal sequences matched well to the deduced sequences, while fragments of the minor vSPs were detected by LC-MS/MS identification. Specific amidolytic activities of the fractions from HPLC and anion exchange separation were assayed using four chromogenic substrates, respectively. Molecular phylogenetic tree based on the sequences of these vSPs and their orthologs revealed six major clusters, one of them covered four lineages of plasminogen activator like vSPs. N-glycosylation patterns and variations for the vSPs are discussed. The high sequence similarities between G. intermedius vSPs and their respective orthologs from American pitvipers suggest that most of the isoforms evolved before Asian pitvipers migrated to the New World. Our results also indicate that the neurotoxic venoms contain more kallikrein-like vSPs and hypotensive components than the hemorrhagic venoms. Full sequences and expression levels of nine paralogous serine proteases (designated as GiSPs) of Gloydius intermedius venom have been studied. A kallikrein-like enzyme is most abundant and four isoforms homologous to venom plasminogen-activators are also expressed in this venom. Taken together, the present and previous data demonstrate that the neurotoxic G. intermedius venoms contain more hypotensive vSPs relative to other hemorrhagic pitviper venoms and the pitviper vSPs are highly versatile and diverse. Their structure-function relationships remain to be explored and

Mental state, body image disturbances and social competences in adolescents with strabismus

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Cecylia Smug

2010-06-01

Full Text Available Introduction: Strabismus is a serious ophthalmological and cosmetic disorder which may cause psychological discomfort. An increased incidence of various mental disturbances in patients with squint has been described. Affected children and adolescents experience more difficulties at school and worse results in sport. Squint may cause a disadvantageous social reception and may sometimes make it difficult to get a satisfying job. It may considerably decrease the quality of life. Objective: This study addressed three questions: 1 Is strabismus linked to psychiatric and psychological disorders? 2 Can it influence social competences? 3 Is it linked to dysmorphophobia (DSM-IV? Material and methods: Thirty persons with strabismus at the age of 13-17 years were compared with the control group of 30 persons of the same age, without eye problems. To detect psychiatric problems GHQ-28 scale was used. To assess social competences the Social Competence Questionnaire KKS (Kwestionariusz Kompetencji Społecznych was used. Dysmorphophobia symptoms were measured using the Body Dysmorphic Disorder Examination (BDDE. Results: There were no statistically significant differences in the incidence of symptoms of depression, anxiety, sleep disorders, functioning, social competences or dysmorphophobia in adolescents with strabismus, as compared to the control group. Significantly worse social competences were shown by those adolescents with strabismus who underwent surgical treatment, as compared to other persons with squint (p=0.006. Discussion: In literature, we have not found any studies on social competences in young people with strabismus. The prevalence of dysmorphophobia was not confirmed among them. No higher incidence of psychiatric disorders was observed in our study in adolescents with strabismus.

Geometric Theory of Heat from Souriau Lie Groups Thermodynamics and Koszul Hessian Geometry: Applications in Information Geometry for Exponential Families

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Frédéric Barbaresco

2016-11-01

Full Text Available We introduce the symplectic structure of information geometry based on Souriau’s Lie group thermodynamics model, with a covariant definition of Gibbs equilibrium via invariances through co-adjoint action of a group on its moment space, defining physical observables like energy, heat, and moment as pure geometrical objects. Using geometric Planck temperature of Souriau model and symplectic cocycle notion, the Fisher metric is identified as a Souriau geometric heat capacity. The Souriau model is based on affine representation of Lie group and Lie algebra that we compare with Koszul works on G/K homogeneous space and bijective correspondence between the set of G-invariant flat connections on G/K and the set of affine representations of the Lie algebra of G. In the framework of Lie group thermodynamics, an Euler-Poincaré equation is elaborated with respect to thermodynamic variables, and a new variational principal for thermodynamics is built through an invariant Poincaré-Cartan-Souriau integral. The Souriau-Fisher metric is linked to KKS (Kostant–Kirillov–Souriau 2-form that associates a canonical homogeneous symplectic manifold to the co-adjoint orbits. We apply this model in the framework of information geometry for the action of an affine group for exponential families, and provide some illustrations of use cases for multivariate gaussian densities. Information geometry is presented in the context of the seminal work of Fréchet and his Clairaut-Legendre equation. The Souriau model of statistical physics is validated as compatible with the Balian gauge model of thermodynamics. We recall the precursor work of Casalis on affine group invariance for natural exponential families.

MIGRATION OF PHTHALATES FROM PLASTIC TANK TO VEGETABLE OIL AS A PART OF FEEDING MIXTURES USED FOR CHICKEN BROILERS FATTENING

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Pavel Suchý

2010-05-01

Full Text Available The concentrations of phthalic acid esters (PAEs as di-n-butyl phthalate (DBP and di-2-ethylhexyl phthalate (DEHP were measured in samples of rapeseed oil, which was used as a feed. First samples were collected during the production process and second after the storage in plastic tank (21 days. The results of measurements are that there is 2.93-10.10 mg PAEs.kg-1 in the oil before storage and 22.73-61.55 mg PAEs.kg-1 after storage. For the monitoring of distribution and accumulation of PAEs in animal tissues and organs (muscles, adipose tissue, skin and liver broiler chicks ROSS 308 were used. The chicks were divided into 4 groups (50 chicks each. All the chicks were fed by commercial diets (complete feed, KKS for broiler chicks (starter – BR1; grower – BR2 and finisher – BR3. The experimental diets were supplemented with vegetable oil (RO with low (group N or high (group V phthalate content, or animal fat with high phthalate content (group Z. Neither the control diets (K nor the grower (BR1 diets contained vegetable oil or animal fat. DBP and DEHP were found in all tissues of all chicks. The highest concentration of DBP of 1.28 1.00 mg.kg-1 of fresh sample (an average value from 8 chicks was determined in the adipose tissue of V chicks. The highest concentration of DEHP of 3.27 2.87 mg.kg-1 of fresh sample (average of 8 chicks was also determined in the V group. doi:10.5219/49

Clinical Features, Presence of Human Herpesvirus-8 and Treatment Results in Classic Kaposi Sarcoma

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Özlem Su

2008-12-01

Full Text Available Background and Design: Classic Kaposi sarcoma (KS occurs predominantly among the elderly, with Jews, Italians and Greeks. Classic KS has been seen relatively frequently in Turkey. Our aim was to evaluate the demographic, clinical features of Kaposi sarcoma and etiopathological role of human herpesvirus-8 (HHV-8. Treatment results of 18 classic Kaposi’s sarcoma were also concluded.Material and Method: Eighteen cases of classic Kaposi sarcoma diagnosed as clinically and histopathologically between January 2001 and August 2008 in our dermatology department were taken to this study. Demographic, clinical features and treatment results were reviewed retrospectively in all patients. HHV-8 was investigated in the lesional skin of 7 patients.Results: A male/female ratio of 2/1 was found. Mean age at diagnosis was 67.2 (37-94 years. Bilaterally lower extremities were involved in 15 patients (83.3%, the trunk was involved in 3 patients (16.6%. Plaques and nodules were the common type of lesions (66.6% and 55.5%. Nine patients had no symptoms (50%. Edema was the most common symptom (38.8%. A second primary malignancy was found in 2 patients (11.1%. HHV-8 was detected in 6 of the 7 patients(85.7%. Majority of the patients were treated with interferon alfa (subcutaneously and cryotherapy as a monotherapy or a combination therapy. Imiquimod was the second agent in combined treatment (27.7%. Conclusion: We suggest that interferon alfa and imiquimod can be used as first line therapy agents with their antiviral and immunmodulatuar features in the treatment of KKS. (Turkderm 2008; 42: 122-6

Finite-deformation phase-field chemomechanics for multiphase, multicomponent solids

Science.gov (United States)

Svendsen, Bob; Shanthraj, Pratheek; Raabe, Dierk

2018-03-01

The purpose of this work is the development of a framework for the formulation of geometrically non-linear inelastic chemomechanical models for a mixture of multiple chemical components diffusing among multiple transforming solid phases. The focus here is on general model formulation. No specific model or application is pursued in this work. To this end, basic balance and constitutive relations from non-equilibrium thermodynamics and continuum mixture theory are combined with a phase-field-based description of multicomponent solid phases and their interfaces. Solid phase modeling is based in particular on a chemomechanical free energy and stress relaxation via the evolution of phase-specific concentration fields, order-parameter fields (e.g., related to chemical ordering, structural ordering, or defects), and local internal variables. At the mixture level, differences or contrasts in phase composition and phase local deformation in phase interface regions are treated as mixture internal variables. In this context, various phase interface models are considered. In the equilibrium limit, phase contrasts in composition and local deformation in the phase interface region are determined via bulk energy minimization. On the chemical side, the equilibrium limit of the current model formulation reduces to a multicomponent, multiphase, generalization of existing two-phase binary alloy interface equilibrium conditions (e.g., KKS). On the mechanical side, the equilibrium limit of one interface model considered represents a multiphase generalization of Reuss-Sachs conditions from mechanical homogenization theory. Analogously, other interface models considered represent generalizations of interface equilibrium conditions consistent with laminate and sharp-interface theory. In the last part of the work, selected existing models are formulated within the current framework as special cases and discussed in detail.

Pain and microcrystalline arthritis

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R. Ramonda

2014-06-01

Full Text Available Microcrystals are responsible for some of the most common and complex arthropathies which are often accompanied by intense, severe pain and inflammatory reactions. The main pathogens are crystals of monosodium urate (MSU, responsible for the gout, calcium pyrophosphate (CPP, which deposits also in various clinical forms of arthopathies, and basic calcium phosphate associated with osteoarthritis. In this context, the microcrystal arthritis is characterized by multiple, acute attacks followed by chronic pain, disability, impaired quality of life, and increased mortality. Given their chronic nature, they represent an ever more urgent public health problem. MSU and CPP crystals are also able to activate nociceptors. The pain in mycrocrystalline arthritis (MCA is an expression of the inflammatory process. In the course of these diseases there is an abundant release of inflammatory molecules, including prostaglandins 2 and kinins. Interleukin-1 represents the most important cytokine released during the crystal-induced inflammatory process. Therefore, clinically, pain is the most important component of MCA, which lead to functional impairment and disability in a large proportion of the population. It is fundamental to diagnose these diseases as early as possible, and to this aim, to identify appropriate and specific targets for a timely therapeutic intervention.

Evlilik İçi Zorla Cinsel İlişki Üzerine Bir Anket Çalışması

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Mehmet Fatih Yavuz

1998-08-01

Full Text Available Bu çalışmada, 170’i hukuk mezunu, 480’i toplumun çeşitli kesimlerinden olmak üzere toplam 650 kişinin evlilikiçi zorla cinsel ilişki konusundaki görüşlerini belirleyen anket formlarının sonuçları değerlendirilmiştir. Çalışmaya katılanların % 65’inin, hukukçuların % 45’inin ve toplumdan katılanların % 71’inin kocanın karısıyla zorla cinsel ilişkide bulunmasının bir ırza geçme suçu oluşturacağına inandıkları görülmektedir.Çalışmaya katılanların yarıdan fazlasının bu görüşte olması evlilikiçi zorla cinsel ilişkinin ırza geçme suçu olarak düzenlenmesi yolundaki tartışmalara basamak oluşturmaktadır. Anahtar kelimeler: Evlilik, Irza geçme.

Effect of nephrotoxic treatment with gentamicin on rats chronically exposed to uranium

International Nuclear Information System (INIS)

Rouas, Caroline; Stefani, Johanna; Grison, Stephane; Grandcolas, Line; Baudelin, Cedric; Dublineau, Isabelle; Pallardy, Marc; Gueguen, Yann

2011-01-01

Uranium is a radioactive heavy metal with a predominantly chemical toxicity, affecting especially the kidneys and more particularly the proximal tubular structure. Until now, few experimental studies have examined the effect of chronic low-dose exposure to uranium on kidney integrity: these mainly analyse standard markers such as creatinine and urea, and none has studied the effect of additional co-exposure to a nephrotoxic agent on rats chronically exposed to uranium. The aim of the present study is to examine the potential cumulative effect of treating uranium-exposed rats with a nephrotoxic drug. Neither physiological indicators (diuresis and creatinine clearance) nor standard plasma and urine markers (creatinine, urea and total protein) levels were deteriorated when uranium exposure was combined with gentamicin-induced nephrotoxicity. A histological study confirmed the preferential impact of gentamicin on the tubular structure and showed that uranium did not aggravate the histopathological renal lesions. Finally, the use of novel markers of kidney toxicity, such as KIM-1, osteopontin and kallikrein, provides new knowledge about the nephrotoxicity threshold of gentamicin, and allows us to conclude that under our experimental conditions, low dose uranium exposure did not induce signs of nephrotoxicity or enhance renal sensitivity to another nephrotoxicant.

Current drug therapies for rosacea: a chronic vascular and inflammatory skin disease.

Science.gov (United States)

Feldman, Steven R; Huang, William W; Huynh, Tu T

2014-06-01

Rosacea is a chronic skin disorder that presents with abnormal vascular and inflammatory conditions. Clinical manifestations include flushing, facial erythema, inflammatory papules and pustules, telangiectasias, edema, and watery or irritated eyes. To discuss the evolving pathophysiology of rosacea, factors involved in promoting the chronic vascular and inflammatory abnormalities seen in rosacea, and the available drug therapies for the condition. Chronic inflammation and vascular changes are believed to be underlying factors in the pathophysiology of rosacea. Aberrant cathelicidin expression, elevated kallikrein 5 (KLK5) proteolytic activity, and altered toll-like receptor 2 (TLR2) expression have been reported in rosacea skin leading to the production of proinflammatory cytokines. Until recently, drug therapies only targeted the inflammatory lesions (papules and pustules) and transient erythema associated with these inflammatory lesions of rosacea. Brimonidine tartrate gel 0.5% was recently approved for the treatment of persistent (nontransient) facial erythema of rosacea, acting primarily on the cutaneous vascular component of the disease. Rosacea is a chronic vascular and inflammatory skin disease. Understanding the role of factors that trigger the onset of rosacea symptoms and exacerbate the condition is crucial in treating this skin disease.

The Role of Epithelial Stat3 in Amelogenesis during Mouse Incisor Renewal.

Science.gov (United States)

Zhang, Bin; Meng, Bo; Viloria, Edward; Naveau, Adrien; Ganss, Bernhard; Jheon, Andrew H

2018-03-16

The aim of this study was to evaluate the role of epithelial signal transducer and activator of transcription 3 (STAT3) in mouse incisor amelogenesis. Since Stat3 is expressed in the epithelial component of developing and adult mouse teeth, we generated and analyzed Krt14Cre/+;Stat3fl/fl mutant mice in which Stat3 was inactivated in epithelia including ameloblast progenitors and ameloblasts, the cells responsible for enamel formation. Histological analysis showed little enamel matrix in mutant incisors compared to controls. Delayed incisor enamel mineralization was demonstrated using micro-computed X-ray tomography analysis and was supported by an increase in the pre-expression distance of enamel-enriched proteins such as amelogenin, ameloblastin, and kallikrein-4. Lastly, scanning electron microscopy analysis showed little enamel mineralization in mutant incisors underneath the mesial root of the 1st molar; however, the micro-architecture of enamel mineralization was similar in the erupted portion of control and mutant incisors. Taken together, our findings demonstrate for the first time that the absence of epithelial Stat3 in mice leads to delayed incisor amelogenesis. © 2018 S. Karger AG, Basel.

The Single Kinin Receptor Signals to Separate and Independent Physiological Pathways in Malpighian Tubules of the Yellow Fever Mosquito

Science.gov (United States)

2010-06-10

mortar and pestle . On the day of the experiment a female mosquito, 4-7 days post-eclosion, was cold anesthetized and decapitated. Malpighian tubules...tubules was analyzed with the electron probe as described previously (7, 62), except that we used the JEOL JXA 8900 EPMA Microprobe (Tokyo, Japan

Proteolytic degradation of neuropeptide Y (NPY) from head to toe: Identification of novel NPY-cleaving peptidases and potential drug interactions in CNS and Periphery.

Science.gov (United States)

Wagner, Leona; Wolf, Raik; Zeitschel, Ulrike; Rossner, Steffen; Petersén, Åsa; Leavitt, Blair R; Kästner, Florian; Rothermundt, Matthias; Gärtner, Ulf-Torsten; Gündel, Daniel; Schlenzig, Dagmar; Frerker, Nadine; Schade, Jutta; Manhart, Susanne; Rahfeld, Jens-Ulrich; Demuth, Hans-Ulrich; von Hörsten, Stephan

2015-12-01

The bioactivity of neuropeptide Y (NPY) is either N-terminally modulated with respect to receptor selectivity by dipeptidyl peptidase 4 (DP4)-like enzymes or proteolytic degraded by neprilysin or meprins, thereby abrogating signal transduction. However, neither the subcellular nor the compartmental differentiation of these regulatory mechanisms is fully understood. Using mass spectrometry, selective inhibitors and histochemistry, studies across various cell types, body fluids, and tissues revealed that most frequently DP4-like enzymes, aminopeptidases P, secreted meprin-A (Mep-A), and cathepsin D (CTSD) rapidly hydrolyze NPY, depending on the cell type and tissue under study. Novel degradation of NPY by cathepsins B, D, L, G, S, and tissue kallikrein could also be identified. The expression of DP4, CTSD, and Mep-A at the median eminence indicates that the bioactivity of NPY is regulated by peptidases at the interphase between the periphery and the CNS. Detailed ex vivo studies on human sera and CSF samples recognized CTSD as the major NPY-cleaving enzyme in the CSF, whereas an additional C-terminal truncation by angiotensin-converting enzyme could be detected in serum. The latter finding hints to potential drug interaction between antidiabetic DP4 inhibitors and anti-hypertensive angiotensin-converting enzyme inhibitors, while it ablates suspected hypertensive side effects of only antidiabetic DP4-inhibitors application. The bioactivity of neuropeptide Y (NPY) is either N-terminally modulated with respect to receptor selectivity by dipeptidyl peptidase 4 (DP4)-like enzymes or proteolytic degraded by neprilysin or meprins, thereby abrogating signal transduction. However, neither the subcellular nor the compartmental differentiation of these regulatory mechanisms is fully understood. Using mass spectrometry, selective inhibitors and histochemistry, studies across various cell types, body fluids, and tissues revealed that most frequently DP4-like enzymes

Comparison of Venae Sectio vs. modified Seldinger Technique for Totally Implantable Access Ports; Portas-trial [ISRCTN:52368201

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Luntz S

2006-06-01

ür Klinische Studien (KKS – Coordination Centre for Clinical Trails at the University of Heidelberg.

Kuzu Etlerinin Kolesterol ve Yağ İçeriği Arasındaki İlişkinin Saptanması

OpenAIRE

Serdaroğlu, Meltem; Turp, Gülen Yıldız

2000-01-01

Cholesterol is an essential component of animal tissue. Consumers have changed their eating habits as a results of growing concern about cholesterol and amount of daily fat intake. The present study was undertaken to determine the effects of amount of fat and cooking on cholesterol content of various of lamb cuts. As a result no relation was noticed between the fat and cholesterol content of various of lamb cuts. As a result no relation was noticed between the fat and cholesterol content of v...

Optimum Use of Acute Treatments for Hereditary Angioedema: Evidence-Based Expert Consensus

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Hilary Longhurst

2018-03-01

Full Text Available Acute treatment of hereditary angioedema due to C1 inhibitor deficiency has become available in the last 10 years and has greatly improved patients’ quality of life. Two plasma-derived C1 inhibitors (Berinert and Cinryze, a recombinant C1 inhibitor (Ruconest/Conestat alpha, a kallikrein inhibitor (Ecallantide, and a bradykinin B2 receptor inhibitor (Icatibant are all effective. Durably good response is maintained over repeated treatments and several years. All currently available prophylactic agents are associated with breakthrough attacks, therefore an acute treatment plan is essential for every patient. Experience has shown that higher doses of C1 inhibitor than previously recommended may be desirable, although only recombinant C1 inhibitor has been subject to full dose–response evaluation. Treatment of early symptoms of an attack, with any licensed therapy, results in milder symptoms, more rapid resolution and shorter duration of attack, compared with later treatment. All therapies have been shown to be well-tolerated, with low risk of serious adverse events. Plasma-derived C1 inhibitors have a reassuring safety record regarding lack of transmission of virus or other infection. Thrombosis has been reported in association with plasma-derived C1 inhibitor in some case series. Ruconest was associated with anaphylaxis in a single rabbit-allergic volunteer, but no further anaphylaxis has been reported in those not allergic to rabbits despite, in a few cases, prior IgE sensitization to rabbit or milk protein. Icatibant is associated with high incidence of local reactions but not with systemic effects. Ecallantide may cause anaphylactoid reactions and is given under supervision. For children and pregnant women, plasma-derived C1 inhibitor has the best evidence of safety and currently remains first-line treatment.

Optimum Use of Acute Treatments for Hereditary Angioedema: Evidence-Based Expert Consensus.

Science.gov (United States)

Longhurst, Hilary

2017-01-01

Acute treatment of hereditary angioedema due to C1 inhibitor deficiency has become available in the last 10 years and has greatly improved patients' quality of life. Two plasma-derived C1 inhibitors (Berinert and Cinryze), a recombinant C1 inhibitor (Ruconest/Conestat alpha), a kallikrein inhibitor (Ecallantide), and a bradykinin B2 receptor inhibitor (Icatibant) are all effective. Durably good response is maintained over repeated treatments and several years. All currently available prophylactic agents are associated with breakthrough attacks, therefore an acute treatment plan is essential for every patient. Experience has shown that higher doses of C1 inhibitor than previously recommended may be desirable, although only recombinant C1 inhibitor has been subject to full dose-response evaluation. Treatment of early symptoms of an attack, with any licensed therapy, results in milder symptoms, more rapid resolution and shorter duration of attack, compared with later treatment. All therapies have been shown to be well-tolerated, with low risk of serious adverse events. Plasma-derived C1 inhibitors have a reassuring safety record regarding lack of transmission of virus or other infection. Thrombosis has been reported in association with plasma-derived C1 inhibitor in some case series. Ruconest was associated with anaphylaxis in a single rabbit-allergic volunteer, but no further anaphylaxis has been reported in those not allergic to rabbits despite, in a few cases, prior IgE sensitization to rabbit or milk protein. Icatibant is associated with high incidence of local reactions but not with systemic effects. Ecallantide may cause anaphylactoid reactions and is given under supervision. For children and pregnant women, plasma-derived C1 inhibitor has the best evidence of safety and currently remains first-line treatment.

Bioinformatic prediction of arthropod/nematode-like peptides in non-arthropod, non-nematode members of the Ecdysozoa.

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Christie, Andrew E; Nolan, Daniel H; Garcia, Zachery A; McCoole, Matthew D; Harmon, Sarah M; Congdon-Jones, Benjamin; Ohno, Paul; Hartline, Niko; Congdon, Clare Bates; Baer, Kevin N; Lenz, Petra H

2011-02-01

The Onychophora, Priapulida and Tardigrada, along with the Arthropoda, Nematoda and several other small phyla, form the superphylum Ecdysozoa. Numerous peptidomic studies have been undertaken for both the arthropods and nematodes, resulting in the identification of many peptides from each group. In contrast, little is known about the peptides used as paracrines/hormones by species from the other ecdysozoan taxa. Here, transcriptome mining and bioinformatic peptide prediction were used to identify peptides in members of the Onychophora, Priapulida and Tardigrada, the only non-arthropod, non-nematode members of the Ecdysozoa for which there are publicly accessible expressed sequence tags (ESTs). The extant ESTs for each phylum were queried using 106 arthropod/nematode peptide precursors. Transcripts encoding calcitonin-like diuretic hormone and pigment-dispersing hormone (PDH) were identified for the onychophoran Peripatopsis sedgwicki, with transcripts encoding C-type allatostatin (C-AST) and FMRFamide-like peptide identified for the priapulid Priapulus caudatus. For the Tardigrada, transcripts encoding members of the A-type allatostatin, C-AST, insect kinin, orcokinin, PDH and tachykinin-related peptide families were identified, all but one from Hypsibius dujardini (the exception being a Milnesium tardigradum orcokinin-encoding transcript). The proteins deduced from these ESTs resulted in the prediction of 48 novel peptides, six onychophoran, eight priapulid and 34 tardigrade, which are the first described from these phyla. Copyright © 2010 Elsevier Inc. All rights reserved.

Indian red scorpion venom-induced augmentation of cardio-respiratory reflexes and pulmonary edema involve the release of histamine.

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Dutta, Abhaya; Deshpande, Shripad B

2011-02-01

Pulmonary edema is a consistent feature of Mesobuthus tamulus (MBT) envenomation. Kinins, prostaglandins and other inflammatory mediators are implicated in it. Since, histamine also increases capillary permeability, this study was undertaken to evaluate whether MBT venom utilizes histamine to produce pulmonary edema and augmentation of cardio-respiratory reflexes evoked by phenylbiguanide (PBG). Blood pressure, respiratory excursions and ECG were recorded in urethane anaesthetized adult rats. Injection of PBG (10 μg/kg) produced apnoea, hypotension and bradycardia and the responses were augmented after exposure to venom (100 μg/kg). There was increased pulmonary water content in these animals. Pretreatment with pheniramine maleate (H₁ antagonist, 3 mg/kg) blocked both venom-induced augmentation of PBG response and pulmonary edema. In another series, compound 48/80 (mast cell depletor) was treated for 4 days then the PBG responses were elicited as before. At the end of the experiments, mast cells were counted from the peritoneal fluid. The venom-induced pulmonary edema and the augmentation of PBG reflex were not observed in compound 48/80 treated animals. Further, mast cells in the peritoneal fluid were absent in this group as compared to vehicle treated group (29 ± 7.9 cells/mm³). These observations indicate that venom-induced pulmonary edema and augmentation of PBG reflexe are mediated through mast cells by involving H₁ receptors. Copyright © 2010 Elsevier Ltd. All rights reserved.

SALO, a novel classical pathway complement inhibitor from saliva of the sand fly Lutzomyia longipalpis.

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Ferreira, Viviana P; Fazito Vale, Vladimir; Pangburn, Michael K; Abdeladhim, Maha; Mendes-Sousa, Antonio Ferreira; Coutinho-Abreu, Iliano V; Rasouli, Manoochehr; Brandt, Elizabeth A; Meneses, Claudio; Lima, Kolyvan Ferreira; Nascimento Araújo, Ricardo; Pereira, Marcos Horácio; Kotsyfakis, Michalis; Oliveira, Fabiano; Kamhawi, Shaden; Ribeiro, Jose M C; Gontijo, Nelder F; Collin, Nicolas; Valenzuela, Jesus G

2016-01-13

Blood-feeding insects inject potent salivary components including complement inhibitors into their host's skin to acquire a blood meal. Sand fly saliva was shown to inhibit the classical pathway of complement; however, the molecular identity of the inhibitor remains unknown. Here, we identified SALO as the classical pathway complement inhibitor. SALO, an 11 kDa protein, has no homology to proteins of any other organism apart from New World sand flies. rSALO anti-complement activity has the same chromatographic properties as the Lu. longipalpis salivary gland homogenate (SGH)counterparts and anti-rSALO antibodies blocked the classical pathway complement activity of rSALO and SGH. Both rSALO and SGH inhibited C4b deposition and cleavage of C4. rSALO, however, did not inhibit the protease activity of C1s nor the enzymatic activity of factor Xa, uPA, thrombin, kallikrein, trypsin and plasmin. Importantly, rSALO did not inhibit the alternative or the lectin pathway of complement. In conclusion our data shows that SALO is a specific classical pathway complement inhibitor present in the saliva of Lu. longipalpis. Importantly, due to its small size and specificity, SALO may offer a therapeutic alternative for complement classical pathway-mediated pathogenic effects in human diseases.

Effect of nephrotoxic treatment with gentamicin on rats chronically exposed to uranium.

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Rouas, Caroline; Stefani, Johanna; Grison, Stéphane; Grandcolas, Line; Baudelin, Cédric; Dublineau, Isabelle; Pallardy, Marc; Gueguen, Yann

2011-01-11

Uranium is a radioactive heavy metal with a predominantly chemical toxicity, affecting especially the kidneys and more particularly the proximal tubular structure. Until now, few experimental studies have examined the effect of chronic low-dose exposure to uranium on kidney integrity: these mainly analyse standard markers such as creatinine and urea, and none has studied the effect of additional co-exposure to a nephrotoxic agent on rats chronically exposed to uranium. The aim of the present study is to examine the potential cumulative effect of treating uranium-exposed rats with a nephrotoxic drug. Neither physiological indicators (diuresis and creatinine clearance) nor standard plasma and urine markers (creatinine, urea and total protein) levels were deteriorated when uranium exposure was combined with gentamicin-induced nephrotoxicity. A histological study confirmed the preferential impact of gentamicin on the tubular structure and showed that uranium did not aggravate the histopathological renal lesions. Finally, the use of novel markers of kidney toxicity, such as KIM-1, osteopontin and kallikrein, provides new knowledge about the nephrotoxicity threshold of gentamicin, and allows us to conclude that under our experimental conditions, low dose uranium exposure did not induce signs of nephrotoxicity or enhance renal sensitivity to another nephrotoxicant. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Overview of hereditary angioedema caused by C1-inhibitor deficiency: assessment and clinical management.

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Bork, K; Davis-Lorton, M

2013-02-01

Hereditary angioedema due to C1-inhibitor deficiency (HAE-C1-INH) is a rare, autosomal-dominant disease. HAE-C1-INH is characterized by recurrent attacks of marked, diffuse, nonpitting and nonpruritic skin swellings, painful abdominal attacks, and laryngeal edema. The extremities and the gastrointestinal tract are most commonly affected. Swelling of the upper respiratory mucosa poses the greatest risk because death from asphyxiation can result from laryngealedema. HAE-C1-INH attacks are variable, unpredictable, and may be induced by a variety of stimuli, including stress or physical trauma. Because the clinical presentation of HAE-C1-INH is similar to other types of angioedema, the condition may be a challenge to diagnose. Accurate identification of HAE-C1-INH is critical in order to avoid asphyxiation by laryngeal edema and to improve the burden of disease. Based on an understanding of the underlying pathophysiology of IHAE-C1-INH, drugs targeted specifically to the disease, such as C1-inhibitor therapy, bradykinin B2-receptor antagonists, and kallikrein-inhibitors, have become available for both treatment and prevention of angioedema attacks. This article reviews the clinical features, differential diagnosis, and current approaches to management of HAE-C1-INH.

Dental Enamel Development: Proteinases and Their Enamel Matrix Substrates

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Bartlett, John D.

2013-01-01

This review focuses on recent discoveries and delves in detail about what is known about each of the proteins (amelogenin, ameloblastin, and enamelin) and proteinases (matrix metalloproteinase-20 and kallikrein-related peptidase-4) that are secreted into the enamel matrix. After an overview of enamel development, this review focuses on these enamel proteins by describing their nomenclature, tissue expression, functions, proteinase activation, and proteinase substrate specificity. These proteins and their respective null mice and human mutations are also evaluated to shed light on the mechanisms that cause nonsyndromic enamel malformations termed amelogenesis imperfecta. Pertinent controversies are addressed. For example, do any of these proteins have a critical function in addition to their role in enamel development? Does amelogenin initiate crystallite growth, does it inhibit crystallite growth in width and thickness, or does it do neither? Detailed examination of the null mouse literature provides unmistakable clues and/or answers to these questions, and this data is thoroughly analyzed. Striking conclusions from this analysis reveal that widely held paradigms of enamel formation are inadequate. The final section of this review weaves the recent data into a plausible new mechanism by which these enamel matrix proteins support and promote enamel development. PMID:24159389

Abrogation of epithelial BMP2 and BMP4 causes Amelogenesis Imperfecta by reducing MMP20 and KLK4 expression.

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Xie, Xiaohua; Liu, Chao; Zhang, Hua; Jani, Priyam H; Lu, Yongbo; Wang, Xiaofang; Zhang, Bin; Qin, Chunlin

2016-05-05

Amelogenesis Imperfecta (AI) can be caused by the deficiencies of enamel matrix proteins, molecules responsible for the transportation and secretion of enamel matrix components, and proteases processing enamel matrix proteins. In the present study, we discovered the double deletion of bone morphogenetic protein 2 (Bmp2) and bone morphogenetic protein 4 (Bmp4) in the dental epithelium by K14-cre resulted in hypoplastic enamel and reduced density in X-ray radiography as well as shortened enamel rods under scanning electron microscopy. Such enamel phenotype was consistent with the diagnosis of hypoplastic amelogenesis imperfecta. Histological and molecular analyses revealed that the removal of matrix proteins in the mutant enamel was drastically delayed, which was coincided with the greatly reduced expression of matrix metalloproteinase 20 (MMP20) and kallikrein 4 (KLK4). Although the expression of multiple enamel matrix proteins was down-regulated in the mutant ameloblasts, the cleavage of ameloblastin was drastically impaired. Therefore, we attributed the AI primarily to the reduction of MMP20 and KLK4. Further investigation found that BMP/Smad4 signaling pathway was down-regulated in the K14-cre;Bmp2(f/f);Bmp4(f/f)ameloblasts, suggesting that the reduced MMP20 and KLK4 expression may be due to the attenuated epithelial BMP/Smad4 signaling.

Chymotrypsin C (Caldecrin) Is Associated with Enamel Development

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Lacruz, R.S.; Smith, C.E.; Smith, S.M.; Hu, P.; Bringas, P.; Sahin-Tóth, M.; Moradian-Oldak, J.; Paine, M.L.

2011-01-01

Two main proteases cleave enamel extracellular matrix proteins during amelogenesis. Matrix metalloprotease-20 (Mmp20) is the predominant enzyme expressed during the secretory stage, while kallikrein-related peptidase-4 (Klk4) is predominantly expressed during maturation. Mutations to both Mmp20 and Klk4 result in abnormal enamel phenotypes. During a recent whole-genome microarray analysis of rat incisor enamel organ cells derived from the secretory and maturation stages of amelogenesis, the serine protease chymotrypsin C (caldecrin, Ctrc) was identified as significantly up-regulated (> 11-fold) during enamel maturation. Prior reports indicate that Ctrc expression is pancreas-specific, albeit low levels were also noted in brain. We here report on the expression of Ctrc in the enamel organ. Quantitative PCR (qPCR) and Western blot analysis were used to confirm the expression of Ctrc in the developing enamel organ. The expression profile of Ctrc is similar to that of Klk4, increasing markedly during the maturation stage relative to the secretory stage, although levels of Ctrc mRNA are lower than for Klk4. The discovery of a new serine protease possibly involved in enamel development has important implications for our understanding of the factors that regulate enamel biomineralization. PMID:21828354

Antithrombotic Potential of Tormentil Extract in Animal Models

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Natalia Marcinczyk

2017-08-01

extract (400 mg/kg significantly reduced platelet activation at the same extent as acetylsalicylic acid. Taken together, we have shown for the first time that tormentil extract inhibits arterial thrombosis in platelet- and endothelial-dependent mechanisms without hemodynamic changes. Further studies on the detailed mechanism of action of tormentil extract toward fibrinolysis and the kinin system should be carried out.

Systems integration (automation system). System integration (automation system)

Energy Technology Data Exchange (ETDEWEB)

Fujii, K; Komori, T; Fukuma, Y; Oikawa, M [Nippon Steal Corp., Tokyo (Japan)

1991-09-26

This paper introduces business activities on an automation systems integration (SI) started by a company in July,1988, and describes the SI concepts. The business activities include, with the CIM (unified production carried out on computers) and AMENITY (living environment) as the mainstays, a single responsibility construction ranging from consultation on structuring optimal systems for processing and assembling industries and intelligent buildings to system design, installation and after-sales services. With an SI standing on users {prime} position taken most importantly, the business starts from a planning and consultation under close coordination. On the conceptual basis of structuring optimal systems using the ompany {prime}s affluent know-hows and tools and adapting and applying with multi-vendors, open networks, centralized and distributed systems, the business is promoted with the accumulated technologies capable of realizing artificial intelligence and neural networks in its background, and supported with highly valuable business results in the past. 10 figs., 1 tab.

Plasma bradykinin and early diabetic nephropathy lesions in type 1 diabetes mellitus.

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Kevin M Wheelock

Full Text Available To examine the association of bradykinin and related peptides with the development of diabetic nephropathy lesions in 243 participants with type 1 diabetes (T1D from the Renin-Angiotensin System Study who, at baseline, were normoalbuminuric, normotensive and had normal or increased glomerular filtration rate (GFR.Plasma concentrations of bradykinin and related peptides were measured at baseline by quantitative mass spectrometry. All participants were randomly assigned at baseline to receive placebo, enalapril or losartan during the 5 years between kidney biopsies. Kidney morphometric data were available from kidney biopsies at baseline and after 5 years. Relationships of peptides with changes in morphometric variables were assessed using multiple linear regression after adjustment for age, sex, diabetes duration, HbA1c, mean arterial pressure, treatment assignment and, for longitudinal analyses, baseline structure.Baseline median albumin excretion rate of study participants was 5.0 μg/min, and mean GFR was 128 mL/min/1.73 m2. After multivariable adjustment, higher plasma concentration of bradykinin (1-8 was associated with greater glomerular volume (partial r = 0.191, P = 0.019 and total filtration surface area (partial r = 0.211, P = 0.010, and higher bradykinin (1-7 and hyp3-bradykinin (1-7 were associated with lower cortical interstitial fractional volume (partial r = -0.189, P = 0.011; partial r = -0.164, P = 0.027 respectively. In longitudinal analyses, higher bradykinin was associated with preservation of surface density of the peripheral glomerular basement membrane (partial r = 0.162, P = 0.013, and for participants randomized to losartan, higher hyp3-bradykinin (1-8 was associated with more limited increase in cortical interstitial fractional volume (partial r = -0.291, P = 0.033.Higher plasma bradykinin and related peptide concentrations measured before clinical onset of diabetic nephropathy in persons with T1D were associated with

Distribution of voltage-dependent and intracellular Ca2+ channels in submucosal neurons from rat distal colon.

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Rehn, Matthias; Bader, Sandra; Bell, Anna; Diener, Martin

2013-09-01

We recently observed a bradykinin-induced increase in the cytosolic Ca2+ concentration in submucosal neurons of rat colon, an increase inhibited by blockers of voltage-dependent Ca2+ (Ca(v)) channels. As the types of Ca(v) channels used by this part of the enteric nervous system are unknown, the expression of various Ca(v) subunits has been investigated in whole-mount submucosal preparations by immunohistochemistry. Submucosal neurons, identified by a neuronal marker (microtubule-associated protein 2), are immunoreactive for Ca(v)1.2, Ca(v)1.3 and Ca(v)2.2, expression being confirmed by reverse transcription plus the polymerase chain reaction. These data agree with previous observations that the inhibition of L- and N-type Ca2+ currents strongly inhibits the response to bradykinin. However, whole-cell patch-clamp experiments have revealed that bradykinin does not enhance Ca2+ inward currents under voltage-clamp conditions. Consequently, bradykinin does not directly interact with Ca(v) channels. Instead, the kinin-induced Ca2+ influx is caused indirectly by the membrane depolarization evoked by this peptide. As intracellular Ca2+ channels on Ca(2+)-storing organelles can also contribute to Ca2+ signaling, their expression has been investigated by imaging experiments and immunohistochemistry. Inositol 1,4,5-trisphosphate (IP3) receptors (IP3R) have been functionally demonstrated in submucosal neurons loaded with the Ca(2+)-sensitive fluorescent dye, fura-2. Histamine, a typical agonist coupled to the phospholipase C pathway, induces an increase in the fura-2 signal ratio, which is suppressed by 2-aminophenylborate, a blocker of IP3 receptors. The expression of IP3R1 has been confirmed by immunohistochemistry. In contrast, ryanodine, tested over a wide concentration range, evokes no increase in the cytosolic Ca2+ concentration nor is there immunohistochemical evidence for the expression of ryanodine receptors in these neurons. Thus, rat submucosal neurons are equipped

Psoriatic arthritis

International Nuclear Information System (INIS)

Sankowski, Artur Jacek; Łebkowska, Urszula Maria; Ćwikła, Jarosław; Walecka, Irena; Walecki, Jerzy

2013-01-01

Psoriatic arthritis (PsA) is a chronic inflammatory joint disease which develops in patients with psoriasis. It is characteristic that the rheumatoid factor in serum is absent. Etiology of the disease is still unclear but a number of genetic associations have been identified. Inheritance of the disease is multilevel and the role of environmental factors is emphasized. Immunology of PsA is also complex. Inflammation is caused by immunological reactions leading to release of kinins. Destructive changes in bones usually appear after a few months from the onset of clinical symptoms. Typically PsA involves joints of the axial skeleton with an asymmetrical pattern. The spectrum of symptoms include inflammatory changes in attachments of articular capsules, tendons, and ligaments to bone surface. The disease can have divers clinical course but usually manifests as oligoarthritis. Imaging plays an important role in the diagnosis of PsA. Classical radiography has been used for this purpose for over a hundred years. It allows to identify late stages of the disease, when bone tissue is affected. In the last 20 years many new imaging modalities, such as ultrasonography (US), computed tomography (CT) and magnetic resonance (MR), have been developed and became important diagnostic tools for evaluation of rheumatoid diseases. They enable the assessment and monitoring of early inflammatory changes. As a result, patients have earlier access to modern treatment and thus formation of destructive changes in joints can be markedly delayed or even avoided

Tc-99m Glu-Cys-Gly-His-Gly-Lys (ECG-HGK), a novel Tc-99m labeled hexapeptide for molecular tumor imaging.

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Kim, Dae-Weung; Kim, Myoung Hyoun; Kim, Chang Guhn

2016-03-01

Domain 5 of kinin-free high molecular weight kininogen inhibits the adhesion of many tumor cell lines, and it has been reported that the histidine-glycine-lysine (HGK)-rich region might be responsible for inhibition of cell adhesion. The authors developed HGK-containing hexapeptide, glutamic acid-cysteine-glycine (ECG)-HGK, and evaluated the utility of Tc-99m ECG-HGK for tumor imaging. Hexapeptide, ECG-HGK was synthesized using Fmoc solid-phase peptide synthesis. Radiolabeling efficiency was evaluated. The uptake of Tc-99m ECG-HGK within HT-1080 cells was evaluated in vitro. In HT-1080 tumor-bearing mice, gamma imaging and biodistribution studies were performed. The complexes Tc-99m ECG-HGK was prepared in high yield. The uptake of Tc-99m ECG-HGK within the HT-1080 tumor cells had been demonstrated by in vitro studies. The gamma camera imaging in the murine model showed that Tc-99m ECG-HGK was accumulated substantially in the HT-1080 tumor (tumor-to-muscle ratio = 5.7 ± 1.4 at 4 h), and the tumoral uptake was blocked by the co-injection of excess HGK (tumor-to-muscle ratio = 2.8 ± 0.6 at 4 h). In the present study, Tc-99m ECG-HGK was developed as a new tumor imaging agents. Our in vitro and in vivo studies revealed specific function of Tc-99m ECG-HGK for tumor imaging. Copyright © 2016 John Wiley & Sons, Ltd.

İş Hayatında Tükenmişlik Sendromu: Finans ve Muhasebe Çalışanlarının Tükenmişlik Düzeylerinin Belirlenmesine İlişkin Bir Çalışma

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Elvan OKUTAN

2013-09-01

Full Text Available Çalışmanın amacı, KOBİ’lerin Finans ve Mali İşler Departmanı'nda çalışan muhasebe ve finans elemanlarının tükenmişlik düzeyinin belirlenmesi ve tükenmişlik düzeyleri ile demografik özellikleri arasındaki ilişkinin tespit edilmesidir. Araştırma kapsamında uygulanan ankette, Maslach Tükenmişlik ölçeği kullanılmıştır. Elde edilen veriler SPSS 15 kullanılarak frekans değerleri, t-testi ve ANOVA testi yardımıyla analiz edilmiştir. Araştırmadan elde edilen bulgular değerlendirildiğinde genel olarak araştırma kapsamındaki meslek elemanlarının duygusal tükenme düzeylerinin düşük, duyarsızlaşma düzeylerinin normal, kişisel başarı düzeylerinin ise yüksek olduğu saptanmıştır. Bu bağlamda, yapılan araştırma kapsamında muhasebe ve finans çalışanlarının düşük tükenme düzeylerine sahip oldukları ifade edilebilir.

Influence of growth regulators (IBA, BA on anatomical and morphological changes in bromeliads in in vitro culture

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Renata Galek

2014-01-01

Full Text Available The subject of study were Tillandsia coronata and Guzmania monostachya. The material has been obtained by means of in vitro propagation. The plants were grown for 18 weeks on various kinds of media. Morphological changes were recorded in both species subjected to action of growth regulators. The changes in plant habit were linked with anatomic build. The effect of cytokinin BA upon growth of the stem pith was found, transversely to its axis, through development of numerous meristematic centres and growth and development of adventitious shoots. Leaves of plant grown on media containing cyto-kinin BA were build of a higher number of cell layers of assimilation parenchyma. In plants grown on media with addition of cytokinin the size of stomatal cells was smaller and was accompanied by analogous changes in size of epidermis cells proper. The bushy type of the plants, caused by presence of cytokinin in medium, resulted from the increase of thickness and breadth of leaves and growth of the stem pith, with simultaneous inhibition of cells' elongation. Auxin IBA did not favour the growth of the existing axillary shoots, but stimulated elongation of the stem pith. The stomata of plants of both species grown on media with addition of auxin were bigger. As result of the applied growth regulators a higher frequency of appearance of binucleate cells was found in parenchyma cells of the stem and leaves in both the species studied.

Mechanisms of endothelial dysfunction in resistance arteries from patients with end-stage renal disease.

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Leanid Luksha

Full Text Available The study focuses on the mechanisms of endothelial dysfunction in the uremic milieu. Subcutaneous resistance arteries from 35 end-stage renal disease (ESRD patients and 28 matched controls were studied ex-vivo. Basal and receptor-dependent effects of endothelium-derived factors, expression of endothelial NO synthase (eNOS, prerequisites for myoendothelial gap junctions (MEGJ, and associations between endothelium-dependent responses and plasma levels of endothelial dysfunction markers were assessed. The contribution of endothelium-derived hyperpolarizing factor (EDHF to endothelium-dependent relaxation was impaired in uremic arteries after stimulation with bradykinin, but not acetylcholine, reflecting the agonist-specific differences. Diminished vasodilator influences of the endothelium on basal tone and enhanced plasma levels of asymmetrical dimethyl L-arginine (ADMA suggest impairment in NO-mediated regulation of uremic arteries. eNOS expression and contribution of MEGJs to EDHF type responses were unaltered. Plasma levels of ADMA were negatively associated with endothelium-dependent responses in uremic arteries. Preserved responses of smooth muscle to pinacidil and NO-donor indicate alterations within the endothelium and tolerance of vasodilator mechanisms to the uremic retention products at the level of smooth muscle. We conclude that both EDHF and NO pathways that control resistance artery tone are impaired in the uremic milieu. For the first time, we validate the alterations in EDHF type responses linked to kinin receptors in ESRD patients. The association between plasma ADMA concentrations and endothelial function in uremic resistance vasculature may have diagnostic and future therapeutic implications.

Coupling component systems towards systems of systems

OpenAIRE

Autran , Frédéric; Auzelle , Jean-Philippe; Cattan , Denise; Garnier , Jean-Luc; Luzeaux , Dominique; Mayer , Frédérique; Peyrichon , Marc; Ruault , Jean-René

2008-01-01

International audience; Systems of systems (SoS) are a hot topic in our "fully connected global world". Our aim is not to provide another definition of what SoS are, but rather to focus on the adequacy of reusing standard system architecting techniques within this approach in order to improve performance, fault detection and safety issues in large-scale coupled systems that definitely qualify as SoS, whatever the definition is. A key issue will be to secure the availability of the services pr...

Enamel Defects Reflect Perinatal Exposure to Bisphenol A

Science.gov (United States)

Jedeon, Katia; De la Dure-Molla, Muriel; Brookes, Steven J.; Loiodice, Sophia; Marciano, Clémence; Kirkham, Jennifer; Canivenc-Lavier, Marie-Chantal; Boudalia, Sofiane; Bergès, Raymond; Harada, Hidemitsu; Berdal, Ariane; Babajko, Sylvie

2014-01-01

Endocrine-disrupting chemicals (EDCs), including bisphenol A (BPA), are environmental ubiquitous pollutants and associated with a growing health concern. Anecdotally, molar incisor hypomineralization (MIH) is increasing concurrently with EDC-related conditions, which has led us to investigate the effect of BPA on amelogenesis. Rats were exposed daily to BPA from conception until day 30 or 100. At day 30, BPA-affected enamel exhibited hypomineralization similar to human MIH. Scanning electron microscopy and elemental analysis revealed an abnormal accumulation of organic material in erupted enamel. BPA-affected enamel had an abnormal accumulation of exogenous albumin in the maturation stage. Quantitative real-timePCR, Western blotting, and luciferase reporter assays revealed increased expression of enamelin but decreased expression of kallikrein 4 (protease essential for removing enamel proteins) via transcriptional regulation. Data suggest that BPA exerts its effects on amelogenesis by disrupting normal protein removal from the enamel matrix. Interestingly, in 100-day-old rats, erupting incisor enamel was normal, suggesting amelogenesis is only sensitive to MIH-causing agents during a specific time window during development (as reported for human MIH). The present work documents the first experimental model that replicates MIH and presents BPA as a potential causative agent of MIH. Because human enamel defects are irreversible, MIH may provide an easily accessible marker for reporting early EDC exposure in humans. PMID:23764278

Development and immunochemical evaluation of a novel chicken IgY antibody specific for KLK6

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Sotiropoulou Georgia

2012-12-01

Full Text Available Abstract Background Human kallikrein-related peptidase 6 (KLK6 has been implicated in various types of cancer and in neurodegenerative and demyelinating diseases including multiple sclerosis. Further, anti-KLK6 antibodies attenuated disease manifestations in the mouse model of multiple sclerosis. Availability of specific antibodies against KLK6 is fundamental to the development of improved diagnostic and/or immunotherapeutic applications. Here, we exploited the enhanced immunogenicity of mammalian proteins in avian species to generate a polyclonal antibody against KLK6. Results Chicken were immunized with recombinant KLK6 and antibodies Y (IgYs were purified from egg yolk with a simple procedure and evaluated for KLK6 detection by ELISA and Western blot using recombinant proteins and human cell lysates and supernatants. The anti-KLK6 Y polyclonal exhibited high affinity for KLK6 with a detection limit of 30 fmol. On the other hand, the widely used rabbit polyclonal antibody that was raised against the same recombinant KLK6 had a detection limit of 300 fmol. Moreover, the IgYs did not display any crossreactivity with recombinant KLKs or endogenous KLKs and other cellular proteins. Conclusions Based on its high specificity and sensitivity the developed anti-KLK6 IgY is expected to aid the development of improved diagnostic tools for the detection of KLK6 in biological and clinical samples.

Squash inhibitor family of serine proteinases

International Nuclear Information System (INIS)

Otlewski, J.; Krowarsch, D.

1996-01-01

Squash inhibitors of serine proteinases form an uniform family of small proteins. They are built of 27-33 amino-acid residues and cross-linked with three disulfide bridges. The reactive site peptide bond (P1-P1') is between residue 5 (Lys, Arg or Leu) and 6 (always Ile). High resolution X-ray structures are available for two squash inhibitors complexed with trypsin. NMR solution structures have also been determined for free inhibitors. The major structural motif is a distorted, triple-stranded antiparallel beta-sheet. A similar folding motif has been recently found in a number of proteins, including: conotoxins from fish-hunting snails, carboxypeptidase inhibitor from potato, kalata B1 polypeptide, and in some growth factors (e.g. nerve growth factor, transforming growth factor β2, platelet-derived growth factor). Squash inhibitors are highly stable and rigid proteins. They inhibit a number of serine proteinases: trypsin, plasmin, kallikrein, blood clotting factors: X a and XII a , cathepsin G. The inhibition spectrum can be much broadened if specific amino-acid substitutions are introduced, especially at residues which contact proteinase. Squash inhibitors inhibit proteinases via the standard mechanism. According to the mechanism, inhibitors are substrates which exhibit at neutral pH a high k cat /K m index for hydrolysis and resynthesis of the reactive site, and a low value of the hydrolysis constant. (author)

Subcellular distribution of histone-degrading enzyme activities from rat liver

International Nuclear Information System (INIS)

Heinrich, P.C.; Raydt, G.; Puschendorf, B.; Jusic, M.

1976-01-01

Chromatin prepared from liver tissue contains a histone-degrading enzyme activity with a pH optimum of 7.5-8.0, whereas chromatin isolated from purified nuclei is devoid of it. The histone-degrading enzyme activity was assayed with radioactively labelled total histones from Ehrlich ascites tumor cells. Among the different subcellular fractions assayed, only lysosomes and mitochondria exhibited histone-degrading enzymes. A pH optimum around 4.0-5.0 was found for the lysosomal fraction, whereas 7.5-8.0 has been found for mitochondria. Binding studies of frozen and thawed lysosomes or mitochondria to proteinase-free chromatin demonstrate that the proteinase associated with chromatin isolated from frozen tissue originates from damaged mitochondria. The protein degradation patterns obtained after acrylamide gel electrophoresis are similar for the chromatin-associated and the mitochondrial proteinase and different from that obtained after incubation with lysosomes. The chromatin-associated proteinase as well as the mitochondrial proteinase are strongly inhibited by 1.0 mM phenylmethanesulfonyl fluoride. Weak inhibition is found for lysosomal proteinases at pH 5. Kallikrein-trypsin inhibitor, however, inhibits lysosomal proteinase activity and has no effect on either chromatin-associated or mitochondrial proteinases. The higher template activity of chromatin isolated from a total homogenate compared to chromatin prepared from nuclei may be due to the presence of this histone-degrading enzyme activity. (orig.) [de

Salt sensitivity: a review with a focus on non-Hispanic blacks and Hispanics

Science.gov (United States)

Richardson, Safiya I.; Freedman, Barry I.; Ellison, David H.; Rodriguez, Carlos J.

2015-01-01

The purpose of this review is to summarize the available information regarding salt sensitivity particularly as it relates to non-Hispanic blacks and Hispanics and to clarify possible etiologies, especially those that might shed light on potential treatment options. In non-Hispanic blacks, there is evidence that endothelial dysfunction, reduced potassium intake, decreased urinary kallikrein excretion, upregulation of sodium channel activity, dysfunction in atrial natriuretic peptide (ANP) production, and APOL1 gene nephropathy risk variants may cause or contribute to salt sensitivity. Supported treatment avenues include diets high in potassium and soybean protein, the components of which stimulate nitric oxide production. Racial heterogeneity complicates the study of salt sensitivity in Hispanic populations. Caribbean Hispanics, who have a higher proportion of African ancestry, may respond to commonly prescribed anti-hypertensive agents in a way that is characteristic of non-Hispanic black hypertensives. The low-renin hypertensive phenotype commonly seen in non-Hispanic blacks has been linked to salt sensitivity and may indicate an increased risk for salt sensitivity in a portion of the Hispanic population. In conclusion, increased morbidity and mortality associated with salt sensitivity mandates further studies evaluating the efficacy of tailored dietary and pharmacologic treatment in non-Hispanic blacks and determining the prevalence of low renin hypertension and salt sensitivity within the various subgroups of Hispanic Americans. PMID:23428408

Intact cell MALDI-TOF mass spectrometry on single bovine oocyte and follicular cells combined with top-down proteomics: A novel approach to characterise markers of oocyte maturation.

Science.gov (United States)

Labas, Valérie; Teixeira-Gomes, Ana-Paula; Bouguereau, Laura; Gargaros, Audrey; Spina, Lucie; Marestaing, Aurélie; Uzbekova, Svetlana

2018-03-20

Intact cell MALDI-TOF mass spectrometry (ICM-MS) was adapted to bovine follicular cells from individual ovarian follicles to obtain the protein/peptide signatures (top-down workflow using high resolution MS/MS (TD HR-MS) was performed on the protein extracts from oocytes, CC and GC. The TD HR-MS proteomic approach allowed for: (1) identification of 386 peptide/proteoforms encoded by 194 genes; and (2) characterisation of proteolysis products likely resulting from the action of kallikreins and caspases. In total, 136 peaks observed by ICM-MS were annotated by TD HR-MS (ProteomeXchange PXD004892). Among these, 16 markers of maturation were identified, including IGF2 binding protein 3 and hemoglobin B in the oocyte, thymosins beta-4 and beta-10, histone H2B and ubiquitin in CC. The combination of ICM-MS and TD HR-MS proved to be a suitable strategy to identify non-invasive markers of oocyte quality using limited biological samples. Intact cell MALDI-TOF mass spectrometry on single oocytes and their surrounding cumulus cells, coupled to an optimised top-down HR-MS proteomic approach on ovarian follicular cells, was used to identify specific markers of oocyte meiotic maturation represented by whole low molecular weight proteins or products of degradation by specific proteases. Copyright © 2017 Elsevier B.V. All rights reserved.

Buffering of protons released by mineral formation during amelogenesis in mice.

Science.gov (United States)

Bronckers, Antonius L J J; Lyaruu, Don M; Jalali, Rozita; DenBesten, Pamela K

2016-10-01

Regulation of pH by ameloblasts during amelogenesis is critical for enamel mineralization. We examined the effects of reduced bicarbonate secretion and the presence or absence of amelogenins on ameloblast modulation and enamel mineralization. To that end, the composition of fluorotic and non-fluorotic enamel of several different mouse mutants, including enamel of cystic fibrosis transmembrane conductance regulator-deficient (Cftr null), anion exchanger-2-deficient (Ae2a,b null), and amelogenin-deficient (Amelx null) mice, was determined by quantitative X-ray microanalysis. Correlation analysis was carried out to compare the effects of changes in the levels of sulfated-matrix (S) and chlorine (Cl; for bicarbonate secretion) on mineralization and modulation. The chloride (Cl - ) levels in forming enamel determined the ability of ameloblasts to modulate, remove matrix, and mineralize enamel. In general, the lower the Cl - content, the stronger the negative effects. In Amelx-null mice, modulation was essentially normal and the calcium content was reduced least. Retention of amelogenins in enamel of kallikrein-4-deficient (Klk4-null) mice resulted in decreased mineralization and reduced the length of the first acid modulation band without changing the total length of all acidic bands. These data suggest that buffering by bicarbonates is critical for modulation, matrix removal and enamel mineralization. Amelogenins also act as a buffer but are not critical for modulation. © 2016 Eur J Oral Sci.

Ergenlerin Öznel İyi Oluşlarıyla Aile Ortamları Arasındaki İlişkinin İncelenmesi

OpenAIRE

ERYILMAZ, Yrd. Doç. Dr. Ali

2011-01-01

The Relationship Between Adolescents’ Subjective Well-Being and Family EnvironmentThis study examines the association between family environment and subjective well-being among Turkish adolescents. The participants of the study include a total of 252 adolescents (128 male and 124 female). The ages of them range between 14 and 17. The data of the study were obtained through the use of the Adolescents’ Subjective Well-Being Scale and Family Environment Scale. The data were analyzed through usin...

Digital processing data communication systems (bus systems). Digitale Prozessdaten-Kommunikations-Systeme (Bus Systeme)

Energy Technology Data Exchange (ETDEWEB)

Fleck, K

1980-01-01

After an introduction to the technology of digital processing data communication systems there are the following chapters: digital communication of processing data in automation technology, the technology of biserial communication, the implementaiton of a bus system, the data transmission of the TDC-2000 system of Honeywell's and the process bus CS 275 in the automation system TELEPERM M of Siemens AG.

Protecting information in systems of systems

NARCIS (Netherlands)

Trivellato, D.

2012-01-01

Systems of systems are coalitions of autonomous and heterogeneous systems that collaborate to achieve a common goal. The component systems of a system of systems often belong to different security domains, which are governed by different authorities (hereafter called parties). Furthermore, systems

CHANGES IN THE ANAEROBIC THRESHOLD IN AN ANNUAL CYCLE OF SPORT TRAINING OF YOUNG SOCCER PLAYERS

Directory of Open Access Journals (Sweden)

Robert Śliwowski

2013-04-01

Full Text Available The aim of the study was to assess changes in the anaerobic threshold of young soccer players in an annual training cycle. A group of highly trained 15-18 year old players of KKS Lech Poznań were tested. The tests included an annual training macrocycle, and its individual stages resulted from the time structure of the sports training. In order to assess the level of exercise capacities of the players, a field exercise test of increasing intensity was carried out on a soccer pitch. The test made it possible to determine the 4 millimolar lactate threshold (T LA 4 mmol · l-1 on the basis of the lactate concentration in blood [LA], to establish the threshold running speed and the threshold heart rate [HR]. The threshold running speed at the level of the 4 millimolar lactate threshold was established using the two-point form of the equation of a straight line. The obtained indicators of the threshold running speed allowed for precise establishment of effort intensity used in individual training in developing aerobic endurance. In order to test the significance of differences in mean values between four dates of tests, a non-parametric Friedman ANOVA test was used. The significance of differences between consecutive dates of tests was determined using a post-hoc Friedman ANOVA test. The tests showed significant differences in values of selected indicators determined at the anaerobic threshold in various stages of an annual training cycle of young soccer players. The most beneficial changes in terms of the threshold running speed were noted on the fourth date of tests, when the participants had the highest values of 4.01 m · s-1 for older juniors, and 3.80 m · s-1 for younger juniors. This may be indicative of effective application of an individualized programme of training loads and of good preparation of teams for competition in terms of players’ aerobic endurance.

Data Systems vs. Information Systems

OpenAIRE

Amatayakul, Margret K.

1982-01-01

This paper examines the current status of “hospital information systems” with respect to the distinction between data systems and information systems. It is proposed that the systems currently existing are incomplete data dystems resulting in ineffective information systems.

Situation awareness with systems of systems

CERN Document Server

Tretmans, Jan; Borth, Michael

2013-01-01

This book discusses various aspects, challenges, and solutions for developing systems-of-systems for situation awareness, using applications in the domain of maritime safety and security.  Topics include advanced, multi-objective visualization methods for situation awareness, stochastic outlier selection, rule-based anomaly detection, an ontology-based event model for semantic reasoning, new methods for semi-automatic generation of adapters bridging communication gaps, security policies for systems-of-systems, trust assessment, and methods to deal with the dynamics of systems-of-systems in run-time monitoring, testing, and diagnosis. Architectural considerations for designing information-centric systems-of-systems such as situation awareness systems, and an integrated demonstrator implementing many of the investigated aspects, complete the book.

Intelligent Control Systems with an Introduction to System of Systems Engineering

CERN Document Server

Nanayakkara, Thrishantha

2009-01-01

From aeronautics and manufacturing to healthcare and disaster management, systems engineering (SE) focuses on designing applications that ensure performance optimization. This title integrates the fundamentals of artificial intelligence and systems control in a framework applicable to both simple dynamic systems and large-scale system of systems

Upgraded RECOVER system - CASDAC system

International Nuclear Information System (INIS)

Yamamoto, Yoichi; Koyama, Kinji

1992-03-01

The CASDAC (Containment And Surveillance Data Authenticated Communication) system has been developed by JAERI for nuclear safeguards and physical protection of nuclear material. This system was designed and constructed as an upgraded RECOVER system, design concept of which was based on the original RECOVER system and also the TRANSEAVER system. Both of them were developed several years ago as a remote monitoring system for continual verification of security and safeguards status of nuclear material. The system consists of two subsystems, one of them is a Grand Command Center (GCC) subsystem and the other is a facility subsystem. Communication between the two subsystems is controlled through the international telephone line network. Therefore all communication data are encrypted to prevent access by an unauthorized person who may intend to make a falsification, or tapping. The facility subsystem has an appropriate measure that ensure data security and reliable operation under unattended mode of operator. The software of this system is designed so as to be easily used in other different types of computers. This report describes the outline of the CASDAC system and the results of its performance test. This work has been carried out in the framework of Japan Support Programme for Agency Safeguards (JASPAS) as a project, JA-1. (author)

System design specification Brayton Isotope Power System (BIPS) Flight System (FS), and Ground Demonstration System (GDS)

International Nuclear Information System (INIS)

1976-01-01

The system design specification for ground demonstration, development, and flight qualification of a Brayton Isotope Power System (BIPS) is presented. The requirements for both a BIPS conceptual Flight System (FS) and a Ground Demonstration System (GDS) are defined

Serum biomarker profile associated with high bone turnover and BMD in postmenopausal women.

Science.gov (United States)

Bhattacharyya, Sudeepa; Siegel, Eric R; Achenbach, Sara J; Khosla, Sundeep; Suva, Larry J

2008-07-01

Early diagnosis of the onset of osteoporosis is key to the delivery of effective therapy. Biochemical markers of bone turnover provide a means of evaluating skeletal dynamics that complements static measurements of BMD by DXA. Conventional clinical measurements of bone turnover, primarily the estimation of collagen and its breakdown products in the blood or urine, lack both sensitivity and specificity as a reliable diagnostic tool. As a result, improved tests are needed to augment the use of BMD measurements as the principle diagnostic modality. In this study, the serum proteome of 58 postmenopausal women with high or low/normal bone turnover (training set) was analyzed by surface enhanced laser-desorption/ionization time-of-flight mass spectrometry, and a diagnostic fingerprint was identified using a variety of statistical and machine learning tools. The diagnostic fingerprint was validated in a separate distinct test set, consisting of serum samples from an additional 59 postmenopausal women obtained from the same Mayo cohort, with a gap of 2 yr. Specific protein peaks that discriminate between postmenopausal patients with high or low/normal bone turnover were identified and validated. Multiple supervised learning approaches were able to classify the level of bone turnover in the training set with 80% sensitivity and 100% specificity. In addition, the individual protein peaks were also significantly correlated with BMD measurements in these patients. Four of the major discriminatory peaks in the diagnostic profile were identified as fragments of interalpha-trypsin-inhibitor heavy chain H4 precursor (ITIH4), a plasma kallikrein-sensitive glycoprotein that is a component of the host response system. These data suggest that these serum protein fragments are the serum-borne reflection of the increased osteoclast activity, leading to the increased bone turnover that is associated with decreasing BMD and presumably an increased risk of fracture. In conjunction with the

NEW BIOCHEMICAL MARKERS OF RECURRENCE OF PROSTATE CANCER AFTER HIS TREATMENT

Directory of Open Access Journals (Sweden)

M. B. Chibichyan

2013-01-01

Full Text Available We studied the condition of the blood proteolytic systems (activity of kallikrein (К and level of prekallikrein (PK, the total proteolytic activity of serine proteinases and elastase-like activity, the leukocytic elastase (LE activity, the angiotensin-converting enzyme (ACE activity, and the inhibitor activity of the α1-proteinase inhibitor (α1-PI and α2-macroglobulin (α2-MG in 36 patients after radical prostatectomy (RPE. Group I was composed of 28 patients without biochemical recurrence (BR after RPE. In this group, 18 patients had locally limited cancer, and 10 patients had рТ3. Group II included 8 patients after RPE with development of BR. The prostate cancer stage in Group II was as follows: рT3 in 7 patients, and pT4 in one patient. The average age of the patients in the groups was 61.44±1.39 years. The median PSA before RPE was 8.05 ng/ml (LQ=5.01; UQ=12. The average prostate volume in the groups was 52±2.74 cm3 . The median of observations was 18 months. The control group consisted of 20 healthy males. In Group II patients at 1 month after the RPE, the ACE activity was 136.5% (p1<0.001 higher, and the LE activity was 29.0% (p1<0.05 lower than the corresponding indicators in Group I. The median PSA in Group I at that time was 0.02±0.01 ng/ml, and in Group II it was 0.2±0.04 ng/ml. Thus, increased activity of ACE against the background of the reduced antiproteolytic potential of the blood in patients after RPE is the metabolic basis for development of biochemical recurrence, and can be a marker of its progression. Increased activity of ACE and reduced activity of EA are predictors of BR development as early as at 1 month after RPE, when the PSA level is not yet elevated. 

Profiling Systems Using the Defining Characteristics of Systems of Systems (SoS)

Science.gov (United States)

2010-02-01

system exhaust and emissions system gas engine heating and air conditioning system fuel system regenerative braking system safety system...overcome the limitations of these fuzzy scales, measurement scales are often divided into a relatively small number of disjoint categories so that the...precision is not justified. This lack of precision can typically be addressed by breaking the measurement scale into a set of categories , the use of

Superspeed Maglev system Transrapid. System decription

Energy Technology Data Exchange (ETDEWEB)

Miller, L [Thyssen Henschel AG,, Maglev Transportation Technology, Muenchen (Germany)

1996-12-31

The superspeed maglev system Transrapid is a track-bound transportation system for passengern and priority freight transport. The transrapid trainsets are composed of self-sufficient vehicle section coupled together. The superspeed maglev system Transrapid is capable of revenue operation at speeds of 100 to 500 km/h. Besides the description of the system concept and system characteristics safety and availability are discussed. (HW)

Linking Political Systems and War Systems

DEFF Research Database (Denmark)

Harste, Gorm

2009-01-01

Decisive parts of the Western political system have demonstrated a seemingly surprising misinterpretation of military might. As Madelaine Albright has suggested, the mighty perceived themselves as "almighty". Political power seems to have invested in instrumental coercive power relations and found...... military coercion to be the appropriate mean. Using the system theory and the theory of systemic risks displayed by the German sociologist Niklas Luhmann the article demonstrates how military systems due to their own autonomy and autopoiesis do not fit into the idea of political government....... The Clausewitzian ideal of a political system that could continue its power games by means of war was moderated by Clausewitz' own analysis of "friction". How can a political system be so blind towards the possibilities of another system? What are the risks of systemic blind spots? The argument of the paper...

From systems biology to systems biomedicine.

Science.gov (United States)

Antony, Paul M A; Balling, Rudi; Vlassis, Nikos

2012-08-01

Systems Biology is about combining theory, technology, and targeted experiments in a way that drives not only data accumulation but knowledge as well. The challenge in Systems Biomedicine is to furthermore translate mechanistic insights in biological systems to clinical application, with the central aim of improving patients' quality of life. The challenge is to find theoretically well-chosen models for the contextually correct and intelligible representation of multi-scale biological systems. In this review, we discuss the current state of Systems Biology, highlight the emergence of Systems Biomedicine, and highlight some of the topics and views that we think are important for the efficient application of Systems Theory in Biomedicine. Copyright © 2011 Elsevier Ltd. All rights reserved.

Computer System Design System-on-Chip

CERN Document Server

Flynn, Michael J

2011-01-01

The next generation of computer system designers will be less concerned about details of processors and memories, and more concerned about the elements of a system tailored to particular applications. These designers will have a fundamental knowledge of processors and other elements in the system, but the success of their design will depend on the skills in making system-level tradeoffs that optimize the cost, performance and other attributes to meet application requirements. This book provides a new treatment of computer system design, particularly for System-on-Chip (SOC), which addresses th

The systems integration modeling system

International Nuclear Information System (INIS)

Danker, W.J.; Williams, J.R.

1990-01-01

This paper discusses the systems integration modeling system (SIMS), an analysis tool for the detailed evaluation of the structure and related performance of the Federal Waste Management System (FWMS) and its interface with waste generators. It's use for evaluations in support of system-level decisions as to FWMS configurations, the allocation, sizing, balancing and integration of functions among elements, and the establishment of system-preferred waste selection and sequencing methods and other operating strategies is presented. SIMS includes major analysis submodels which quantify the detailed characteristics of individual waste items, loaded casks and waste packages, simulate the detailed logistics of handling and processing discrete waste items and packages, and perform detailed cost evaluations

System specifications for the NDS Dictionary System

International Nuclear Information System (INIS)

Attree, P.M.; Smith, P.M.

1979-09-01

The NDS Dictionary System is a computerized system for maintaining and distributing the EXFOR dictionaries and for preparing internal versions of these dictionaries for use in the NDS EXFOR System and other NDS systems. This document is an internal manual for the system specifications of the NDS Dictionary System. It includes flow charts, system and program summaries, input and output specifications and file and record descriptions. This manual is updated from time to time when system modifications are made; this is the version of January 1979

Ergenlikte Görülen Problem Davranışlar Ve Aile Sorunları Arasındaki İlişkinin İncelenmesi

OpenAIRE

Arslan, Gökmen; Balkıs, Murat

2014-01-01

The purpose of this study is to investigate relationship between problem behaviors and family problems of adolescents who study in different high school, in Isparta. In this study, participants consist of 581 students (283 female and 298 male), attending different high school in Isparta. Also in this study, problem behaviors and family problems was measured with Risk Behaviors Scale which was developed by Gençtanırım-Kuru (2010) and Family Problems of Young Adulthood Evaluation Scale which wa...

Protecting Information in Systems of Systems

NARCIS (Netherlands)

Trivellato, Daniel; Zannone, Nicola; Etalle, Sandro

2011-01-01

Systems of Systems (SoS) are dynamic, distributed coalitions of autonomous and heterogeneous systems that collaborate to achieve a common goal. While offering several advantages in terms of scalability and flexibility, the SoS paradigm has a strong impact on system interoperability and on the

Expert Systems: What Is an Expert System?

Science.gov (United States)

Duval, Beverly K.; Main, Linda

1994-01-01

Describes expert systems and discusses their use in libraries. Highlights include parts of an expert system; expert system shells; an example of how to build an expert system; a bibliography of 34 sources of information on expert systems in libraries; and a list of 10 expert system shells used in libraries. (Contains five references.) (LRW)

Hot Spot Removal System: System description

Energy Technology Data Exchange (ETDEWEB)

NONE

1997-09-01

Hazardous wastes contaminated with radionuclides, chemicals, and explosives exist across the Department of Energy complex and need to be remediated due to environmental concerns. Currently, an opportunity is being developed to dramatically reduce remediation costs and to assist in the acceleration of schedules associated with these wastes by deploying a Hot Spot Removal System. Removing the hot spot from the waste site will remove risk driver(s) and enable another, more cost effective process/option/remedial alternative (i.e., capping) to be applied to the remainder of the site. The Hot Spot Removal System consists of a suite of technologies that will be utilized to locate and remove source terms. Components of the system can also be used in a variety of other cleanup activities. This Hot Spot Removal System Description document presents technologies that were considered for possible inclusion in the Hot Spot Removal System, technologies made available to the Hot Spot Removal System, industrial interest in the Hot Spot Removal System`s subsystems, the schedule required for the Hot Spot Removal System, the evaluation of the relevant technologies, and the recommendations for equipment and technologies as stated in the Plan section.

Hot Spot Removal System: System description

International Nuclear Information System (INIS)

1997-09-01

Hazardous wastes contaminated with radionuclides, chemicals, and explosives exist across the Department of Energy complex and need to be remediated due to environmental concerns. Currently, an opportunity is being developed to dramatically reduce remediation costs and to assist in the acceleration of schedules associated with these wastes by deploying a Hot Spot Removal System. Removing the hot spot from the waste site will remove risk driver(s) and enable another, more cost effective process/option/remedial alternative (i.e., capping) to be applied to the remainder of the site. The Hot Spot Removal System consists of a suite of technologies that will be utilized to locate and remove source terms. Components of the system can also be used in a variety of other cleanup activities. This Hot Spot Removal System Description document presents technologies that were considered for possible inclusion in the Hot Spot Removal System, technologies made available to the Hot Spot Removal System, industrial interest in the Hot Spot Removal System''s subsystems, the schedule required for the Hot Spot Removal System, the evaluation of the relevant technologies, and the recommendations for equipment and technologies as stated in the Plan section

D0 Cryo System Control System Autodialer

Energy Technology Data Exchange (ETDEWEB)

Urbin, J.; /Fermilab

1990-04-17

The DO cryogenic system is controlled by a TI565-PLC based control system. This allows the system to be unmanned when in steady state operation. System experts will need to be contacted when system parameters exceed normal operating points and reach alarm setpoints. The labwide FIRUS system provides one alarm monitor and communication link. An autodialer provides a second and more flexible alarm monitor and communication link. The autodialer monitors contact points in the control system and after receiving indication of an alarm accesses a list of experts which it calls until it receives an acknowledgement. There are several manufacturers and distributors of autodialer systems. This EN explains the search process the DO cryo group used to fmd an autodialer system that fit the cryo system's needs and includes information and specs for the unit we chose.

Networked control of microgrid system of systems

Science.gov (United States)

Mahmoud, Magdi S.; Rahman, Mohamed Saif Ur; AL-Sunni, Fouad M.

2016-08-01

The microgrid has made its mark in distributed generation and has attracted widespread research. However, microgrid is a complex system which needs to be viewed from an intelligent system of systems perspective. In this paper, a network control system of systems is designed for the islanded microgrid system consisting of three distributed generation units as three subsystems supplying a load. The controller stabilises the microgrid system in the presence of communication infractions such as packet dropouts and delays. Simulation results are included to elucidate the effectiveness of the proposed control strategy.

System program for MICRO-CAMAC terminal system

International Nuclear Information System (INIS)

Sasajima, Yoji; Yamada, Takayuki; Yagi, Hideyuki; Ishiguro, Misako

1979-08-01

A JAERI on-line network system was developed and exists for on-line data processing of nuclear instrumentation. As terminal systems for the network system, the one with a Micro -8 micro-computer is used. By modifying the control program for Micro-8 terminal system, a system program has been developed for a MICRO-CAMAC terminal system, which is controlled by a micro-computer framed within the CAMAC Crate Controller. In this report are described software specifications of the MICRO -CAMAC terminal system and its operation method. (author)

Proteolytic Activity of Prostate-Specific Antigen (PSA) towards Protein Substrates and Effect of Peptides Stimulating PSA Activity

Science.gov (United States)

Mattsson, Johanna M.; Ravela, Suvi; Hekim, Can; Jonsson, Magnus; Malm, Johan; Närvänen, Ale; Stenman, Ulf-Håkan; Koistinen, Hannu

2014-01-01

Prostate-specific antigen (PSA or kallikrein-related peptidase-3, KLK3) exerts chymotrypsin-like proteolytic activity. The main biological function of PSA is the liquefaction of the clot formed after ejaculation by cleavage of semenogelins I and II in seminal fluid. PSA also cleaves several other substrates, which may explain its putative functions in prostate cancer and its antiangiogenic activity. We compared the proteolytic efficiency of PSA towards several protein and peptide substrates and studied the effect of peptides stimulating the activity of PSA with these substrates. An endothelial cell tube formation model was used to analyze the effect of PSA-degraded protein fragments on angiogenesis. We showed that PSA degrades semenogelins I and II much more efficiently than other previously identified protein substrates, e.g., fibronectin, galectin-3 and IGFBP-3. We identified nidogen-1 as a new substrate for PSA. Peptides B2 and C4 that stimulate the activity of PSA towards small peptide substrates also enhanced the proteolytic activity of PSA towards protein substrates. Nidogen-1, galectin-3 or their fragments produced by PSA did not have any effect on endothelial cell tube formation. Although PSA cleaves several other protein substrates, in addition to semenogelins, the physiological importance of this activity remains speculative. The PSA levels in prostate are very high, but several other highly active proteases, such as hK2 and trypsin, are also expressed in the prostate and may cleave protein substrates that are weakly cleaved by PSA. PMID:25237904

Dermasence refining gel modulates pathogenetic factors of rosacea in vitro.

Science.gov (United States)

Borelli, C; Becker, B; Thude, S; Fehrenbacher, B; Isermann, D

2017-12-01

Over the counter cosmetics sold for local treatment of slight to moderate rosacea often state the claim of actively modulating rosacea pathogenesis. Factors involved in the pathogenesis of this common yet complex skin disorder include kallikrein-related peptidase 5 (KLK5), LL-37, as well as protease-activated receptor 2 (PAR2) and vascular endothelial growth factor (VEGF). The objective was to prove the modulating effect of the cosmetic skin care agent Dermasence Refining Gel (DRG) on factors involved in rosacea pathogenesis. We analyzed the effect of DRG on the expression of KLK5, LL-37, PAR2, and VEGF in an in vitro skin model of human reconstituted epidermis. The expression of CAMP (LL-37 gene, fold change -4.19 [±0.11]), VEGFA (fold change -2.55 [±0.12]) and PAR2 (-1.33 [±0.12]) was reduced, KLK5 expression increased (fold change 2.06 (±0.08)) after 18 h of treatment with DRG in comparison to treatment with the matrix gel only. The reduction in CAMP expression was significant (P<.01). The protein expression of all four inflammatory markers was markedly reduced after 18 hours of DRG treatment in comparison to baseline (0 hour), by measure of fluorescence intensity. We show evidence explaining the anti-inflammatory effect of Dermasence Refining Gel in rosacea pathogenesis in vitro. The adjunctive use of DRG in mild to moderate rosacea as a topical cosmetic seems medically reasonable. © 2017 Wiley Periodicals, Inc.

Role of neuropsin in parvalbumin immunoreactivity changes in hippocampal basket terminals of mice reared in various environments

Directory of Open Access Journals (Sweden)

Harumitsu eSuzuki

2014-12-01

Full Text Available In vitro approaches have suggested that neuropsin (or kallikrein 8/KLK8, which controls gamma-aminobutyric acid (GABA neurotransmission through neuregulin-1 and its receptor (ErbB4, is involved in neural plasticity (Tamura et al., 2012, 2013. In the present study, we examined whether parvalbumin (PV-positive neuronal networks, the majority of which are ErbB4-positive GABAergic interneurons, are controlled by neuropsin in tranquil and stimulated voluntarily behaving mice.PV-immunoreactive fibers surrounding hippocampal pyramidal and granular neurons in mice reared in their home cage were decreased in neuropsin-deficient mice, suggesting that neuropsin controls PV immunoreactivity. One- or two-week exposures of wild mice to novel environments, in which they could behave freely and run voluntarily in a wheel resulted in a marked upregulation of both neuropsin mRNA and protein in the hippocampus. To elucidate the functional relevance of the increase in neuropsin during exposure to a rich environment, the intensities of PV-immunoreactive fibers were compared between neuropsin-deficient and wild-type mice under environmental stimuli. When mice were transferred into novel cages (large cages with toys, the intensity of PV-immunoreactive fibers increased in wild-type mice and neuropsin-deficient mice. Therefore, behavioral stimuli control a neuropsin-independent form of PV immunoreactivity. However, the neuropsin-dependent part of the change in PV-immunoreactive fibers may occur in the stimulated hippocampus because increased levels of neuropsin continued during these enriched conditions.

Variability of biological effects of silicas: Different degrees of activation of the fifth component of complement by amorphous silicas

International Nuclear Information System (INIS)

Governa, Mario; Amati, Monica; Fenoglio, Ivana; Valentino, Matteo; Coloccini, Sabrina; Bolognini, Lucia; Carlo Botta, Gian; Emanuelli, Monica; Pierella, Francesca; Volpe, Anna Rita; Astolfi, Paola; Carmignani, Marco; Fubini, Bice

2005-01-01

A biogenic and a pyrogenic amorphous silica were incubated in normal human plasma and compared on a per unit surface basis for their ability to split C5 molecules and yield small C5a peptides. Since C5a peptides induce selective chemotactic attraction of polymorphonuclear leukocytes (PMN), measurement of PMN-induced chemotaxis was used as an index of C5 activation. Though to a lesser extent than the crystalline forms, amorphous silicas can promote the cleavage of C5 protein and generation of C5a-like fragment. The biogenic silica, which differs from the pyrogenic variety in particle shape, level of contaminants, and degree of surface hydrophilicity, besides specific surface, induced a greater response. Both silicas activated C5 through a process which seems to involve multiple events similar to those induced by crystalline silica. C5 molecules are adsorbed and hydroxyl radicals are generated through Haber Weiss cycles catalyzed by the redox-active iron present at the particle surface either as trace impurities or chelated from plasma by silanol groups. In turn, these radicals convert native C5 to an oxidized C5-like form C5(H 2 O 2 ). Finally, C5(H 2 O 2 ) is cleaved by protease enzymatic action of plasma kallikrein activated by the same silica dusts, yielding a product, C5a(H 2 O 2 ), having the same functional characteristic as C5a

Structural Principles in the Development of Cyclic Peptidic Enzyme Inhibitors

Science.gov (United States)

Xu, Peng; Andreasen, Peter A.; Huang, Mingdong

2017-01-01

This review summarizes our studies in the development of small cyclic peptides for specifically modulating enzyme activity. Serine proteases share highly similar active sites but perform diverse physiological and pathological functions. From a phage-display peptide library, we isolated two mono-cyclic peptides, upain-1 (CSWRGLENHRMC) and mupain-1 (CPAYSRYLDC), which inhibit the activity of human and murine urokinase-type plasminogen activators (huPA and muPA) with Ki values in the micromolar or sub-micromolar range, respectively. The following affinity maturations significantly enhanced the potencies of the two peptides, 10-fold and >250-fold for upain-1 and mupain-1, respectively. The most potent muPA inhibitor has a potency (Ki = 2 nM) and specificity comparable to mono-clonal antibodies. Furthermore, we also found an unusual feature of mupain-1 that its inhibitory potency can be enhanced by increasing the flexibility, which challenges the traditional viewpoint that higher rigidity leading to higher affinity. Moreover, by changing a few key residues, we converted mupain-1 from a uPA inhibitor to inhibitors of other serine proteases, including plasma kallikrein (PK) and coagulation factor XIa (fXIa). PK and fXIa inhibitors showed Ki values in the low nanomolar range and high specificity. Our studies demonstrate the versatility of small cyclic peptides to engineer inhibitory potency against serine proteases and to provide a new strategy for generating peptide inhibitors of serine proteases. PMID:29104489

Transition to an Aquatic Habitat Permitted the Repeated Loss of the Pleiotropic KLK8 Gene in Mammals.

Science.gov (United States)

Hecker, Nikolai; Sharma, Virag; Hiller, Michael

2017-11-01

Kallikrein related peptidase 8 (KLK8; also called neuropsin) is a serine protease that plays distinct roles in the skin and hippocampus. In the skin, KLK8 influences keratinocyte proliferation and desquamation, and activates antimicrobial peptides in sweat. In the hippocampus, KLK8 affects memory acquisition. Here, we examined the evolution of KLK8 in mammals and discovered that, out of 70 placental mammals, KLK8 is exclusively lost in three independent fully-aquatic lineages, comprising dolphin, killer whale, minke whale, and manatee. In addition, while the sperm whale has an intact KLK8 reading frame, the gene evolves neutrally in this species. We suggest that the distinct functions of KLK8 likely became obsolete in the aquatic environment, leading to the subsequent loss of KLK8 in several fully-aquatic mammalian lineages. First, the cetacean and manatee skin lacks sweat glands as an adaptation to the aquatic environment, which likely made the epidermal function of KLK8 obsolete. Second, cetaceans and manatees exhibit a proportionally small hippocampus, which may have rendered the hippocampal functions of KLK8 obsolete. Together, our results shed light on the genomic changes that correlate with skin and neuroanatomical differences of aquatic mammals, and show that even pleiotropic genes can be lost during evolution if an environmental change nullifies the need for the different functions of such genes. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Circadian rhythms regulate amelogenesis.

Science.gov (United States)

Zheng, Li; Seon, Yoon Ji; Mourão, Marcio A; Schnell, Santiago; Kim, Doohak; Harada, Hidemitsu; Papagerakis, Silvana; Papagerakis, Petros

2013-07-01

Ameloblasts, the cells responsible for making enamel, modify their morphological features in response to specialized functions necessary for synchronized ameloblast differentiation and enamel formation. Secretory and maturation ameloblasts are characterized by the expression of stage-specific genes which follows strictly controlled repetitive patterns. Circadian rhythms are recognized as key regulators of the development and diseases of many tissues including bone. Our aim was to gain novel insights on the role of clock genes in enamel formation and to explore the potential links between circadian rhythms and amelogenesis. Our data shows definitive evidence that the main clock genes (Bmal1, Clock, Per1 and Per2) oscillate in ameloblasts at regular circadian (24 h) intervals both at RNA and protein levels. This study also reveals that the two markers of ameloblast differentiation i.e. amelogenin (Amelx; a marker of secretory stage ameloblasts) and kallikrein-related peptidase 4 (Klk4, a marker of maturation stage ameloblasts) are downstream targets of clock genes. Both, Amelx and Klk4 show 24h oscillatory expression patterns and their expression levels are up-regulated after Bmal1 over-expression in HAT-7 ameloblast cells. Taken together, these data suggest that both the secretory and the maturation stages of amelogenesis might be under circadian control. Changes in clock gene expression patterns might result in significant alterations of enamel apposition and mineralization. Copyright © 2013 Elsevier Inc. All rights reserved.

Target gene analyses of 39 amelogenesis imperfecta kindreds

Science.gov (United States)

Chan, Hui-Chen; Estrella, Ninna M. R. P.; Milkovich, Rachel N.; Kim, Jung-Wook; Simmer, James P.; Hu, Jan C-C.

2012-01-01

Previously, mutational analyses identified six disease-causing mutations in 24 amelogenesis imperfecta (AI) kindreds. We have since expanded the number of AI kindreds to 39, and performed mutation analyses covering the coding exons and adjoining intron sequences for the six proven AI candidate genes [amelogenin (AMELX), enamelin (ENAM), family with sequence similarity 83, member H (FAM83H), WD repeat containing domain 72 (WDR72), enamelysin (MMP20), and kallikrein-related peptidase 4 (KLK4)] and for ameloblastin (AMBN) (a suspected candidate gene). All four of the X-linked AI families (100%) had disease-causing mutations in AMELX, suggesting that AMELX is the only gene involved in the aetiology of X-linked AI. Eighteen families showed an autosomal-dominant pattern of inheritance. Disease-causing mutations were identified in 12 (67%): eight in FAM83H, and four in ENAM. No FAM83H coding-region or splice-junction mutations were identified in three probands with autosomal-dominant hypocalcification AI (ADHCAI), suggesting that a second gene may contribute to the aetiology of ADHCAI. Six families showed an autosomal-recessive pattern of inheritance, and disease-causing mutations were identified in three (50%): two in MMP20, and one in WDR72. No disease-causing mutations were found in 11 families with only one affected member. We conclude that mutation analyses of the current candidate genes for AI have about a 50% chance of identifying the disease-causing mutation in a given kindred. PMID:22243262

THE URINE PROTEOME FOR RADIATION BIODOSIMETRY: EFFECT OF TOTAL BODY VERSUS LOCAL KIDNEY IRRADIATION

Science.gov (United States)

Sharma, Mukut; Halligan, Brian D.; Wakim, Bassam T.; Savin, Virginia J.; Cohen, Eric P.; Moulder, John E.

2009-01-01

Victims of nuclear accidents or radiological terrorism are likely to receive varying doses of ionizing radiation inhomogeneously distributed over the body. Early biomarkers may be useful in determining organ-specific doses due to total body irradiation (TBI) or partial body irradiation. We used liquid chromatography and mass spectrometry to compare the effect of TBI and local kidney irradiation (LKI) on the rat urine proteome using a single 10 Gy dose of X-rays. Both TBI and LKI altered the urinary protein profile within 24 hours with noticeable differences in Gene Ontology categories. Some proteins including fetuin-B, tissue kallikrein, beta-glucuronidase, vitamin D-dependent calcium binding protein and chondroitin sulfate proteoglycan NG2 were detected only in the TBI group. Some other proteins including major urinary protein-1, RNA binding protein 19, neuron navigator, Dapper homolog 3, WD repeat and FYVE domain containing protein 3, sorting nexin-8, ankycorbin and aquaporin were detected only in the LKI group. Protease inhibitors and kidney proteins were more abundant (fraction of total scans) in the LKI group. Up/Uc ratio and urinary albumin abundance decreased in both TBI and LKI groups. Several markers of acute kidney injury were not detectable in either irradiated group. Present data indicate that abundance and number of proteins may follow opposite trends. These novel findings demonstrate intriguing differences between TBI and LKI, and suggest that urine proteome may be useful in determining organ-specific changes caused by partial body irradiation. PMID:20065682

System design in an evolving system-of-systems architecture and concept of operations

Science.gov (United States)

Rovekamp, Roger N., Jr.

Proposals for space exploration architectures have increased in complexity and scope. Constituent systems (e.g., rovers, habitats, in-situ resource utilization facilities, transfer vehicles, etc) must meet the needs of these architectures by performing in multiple operational environments and across multiple phases of the architecture's evolution. This thesis proposes an approach for using system-of-systems engineering principles in conjunction with system design methods (e.g., Multi-objective optimization, genetic algorithms, etc) to create system design options that perform effectively at both the system and system-of-systems levels, across multiple concepts of operations, and over multiple architectural phases. The framework is presented by way of an application problem that investigates the design of power systems within a power sharing architecture for use in a human Lunar Surface Exploration Campaign. A computer model has been developed that uses candidate power grid distribution solutions for a notional lunar base. The agent-based model utilizes virtual control agents to manage the interactions of various exploration and infrastructure agents. The philosophy behind the model is based both on lunar power supply strategies proposed in literature, as well as on the author's own approaches for power distribution strategies of future lunar bases. In addition to proposing a framework for system design, further implications of system-of-systems engineering principles are briefly explored, specifically as they relate to producing more robust cross-cultural system-of-systems architecture solutions.

Lighting system with thermal management system

Science.gov (United States)

Arik, Mehmet; Weaver, Stanton; Stecher, Thomas; Seeley, Charles; Kuenzler, Glenn; Wolfe, Jr., Charles; Utturkar, Yogen; Sharma, Rajdeep; Prabhakaran, Satish; Icoz, Tunc

2013-05-07

Lighting systems having unique configurations are provided. For instance, the lighting system may include a light source, a thermal management system and driver electronics, each contained within a housing structure. The light source is configured to provide illumination visible through an opening in the housing structure. The thermal management system is configured to provide an air flow, such as a unidirectional air flow, through the housing structure in order to cool the light source. The driver electronics are configured to provide power to each of the light source and the thermal management system.

Intelligent car guidance system (parking support system); Chiteki sharyo yudo system (chusha shien system)

Energy Technology Data Exchange (ETDEWEB)

NONE

2000-03-01

This system enables a driver to park the car at a predetermined spot without the driver seeing the outside scene. The system shows on a driver seat display the steps that the driver is to follow and thereby supports the driver when visibility is poor, when the parking space is difficult to approach, when the driver is a novice, or when the driver is aged. The system ensures accurate positioning of the car by showing the steering direction and angle, the car speed, and the force of braking to the driver. For this purpose, the system knows the absolute car position by the use of an RFID (Radio Frequency Identification) tag which is a kind of IC (Integrated Circuit) card and D-GPS (Differential-Global Positioning System), grasps the relative car position by the use of a gyroscope, and collects data from plural sensors, which are complementary to each other, such as a car-speed sensor and a steering sensor. (translated by NEDO)

SystemC and systemC-AMS in practice systemC 2.3, 2.2 and systemC-AMS 1.0

CERN Document Server

Banerjee, Amal

2013-01-01

This book describes how engineers can make optimum use of the two industry standard analysis/design tools, SystemC and SystemC-AMS.  The authors use a system-level design approach, emphasizing how SystemC and SystemC-AMS features can be exploited most effectively to analyze/understand a given electronic system and explore the design space. The approach taken by this book enables system engineers to concentrate on only those SystemC/SystemC-AMS features that apply to their particular problem, leading to more efficient design. The presentation includes numerous, realistic and complete examples,

Systems engineering for very large systems

Science.gov (United States)

Lewkowicz, Paul E.

Very large integrated systems have always posed special problems for engineers. Whether they are power generation systems, computer networks or space vehicles, whenever there are multiple interfaces, complex technologies or just demanding customers, the challenges are unique. 'Systems engineering' has evolved as a discipline in order to meet these challenges by providing a structured, top-down design and development methodology for the engineer. This paper attempts to define the general class of problems requiring the complete systems engineering treatment and to show how systems engineering can be utilized to improve customer satisfaction and profit ability. Specifically, this work will focus on a design methodology for the largest of systems, not necessarily in terms of physical size, but in terms of complexity and interconnectivity.

Mapping biological systems to network systems

CERN Document Server

Rathore, Heena

2016-01-01

The book presents the challenges inherent in the paradigm shift of network systems from static to highly dynamic distributed systems – it proposes solutions that the symbiotic nature of biological systems can provide into altering networking systems to adapt to these changes. The author discuss how biological systems – which have the inherent capabilities of evolving, self-organizing, self-repairing and flourishing with time – are inspiring researchers to take opportunities from the biology domain and map them with the problems faced in network domain. The book revolves around the central idea of bio-inspired systems -- it begins by exploring why biology and computer network research are such a natural match. This is followed by presenting a broad overview of biologically inspired research in network systems -- it is classified by the biological field that inspired each topic and by the area of networking in which that topic lies. Each case elucidates how biological concepts have been most successfully ...

Man-systems distributed system for Space Station Freedom

Science.gov (United States)

Lewis, J. L.

1990-01-01

Viewgraphs on man-systems distributed system for Space Station Freedom are presented. Topics addressed include: description of man-systems (definition, requirements, scope, subsystems, and topologies); implementation (approach, tools); man-systems interfaces (system to element and system to system); prime/supporting development relationship; selected accomplishments; and technical challenges.

Systems Biology as an Integrated Platform for Bioinformatics, Systems Synthetic Biology, and Systems Metabolic Engineering

Science.gov (United States)

Chen, Bor-Sen; Wu, Chia-Chou

2013-01-01

Systems biology aims at achieving a system-level understanding of living organisms and applying this knowledge to various fields such as synthetic biology, metabolic engineering, and medicine. System-level understanding of living organisms can be derived from insight into: (i) system structure and the mechanism of biological networks such as gene regulation, protein interactions, signaling, and metabolic pathways; (ii) system dynamics of biological networks, which provides an understanding of stability, robustness, and transduction ability through system identification, and through system analysis methods; (iii) system control methods at different levels of biological networks, which provide an understanding of systematic mechanisms to robustly control system states, minimize malfunctions, and provide potential therapeutic targets in disease treatment; (iv) systematic design methods for the modification and construction of biological networks with desired behaviors, which provide system design principles and system simulations for synthetic biology designs and systems metabolic engineering. This review describes current developments in systems biology, systems synthetic biology, and systems metabolic engineering for engineering and biology researchers. We also discuss challenges and future prospects for systems biology and the concept of systems biology as an integrated platform for bioinformatics, systems synthetic biology, and systems metabolic engineering. PMID:24709875

Systems Biology as an Integrated Platform for Bioinformatics, Systems Synthetic Biology, and Systems Metabolic Engineering

Directory of Open Access Journals (Sweden)

Bor-Sen Chen

2013-10-01

Full Text Available Systems biology aims at achieving a system-level understanding of living organisms and applying this knowledge to various fields such as synthetic biology, metabolic engineering, and medicine. System-level understanding of living organisms can be derived from insight into: (i system structure and the mechanism of biological networks such as gene regulation, protein interactions, signaling, and metabolic pathways; (ii system dynamics of biological networks, which provides an understanding of stability, robustness, and transduction ability through system identification, and through system analysis methods; (iii system control methods at different levels of biological networks, which provide an understanding of systematic mechanisms to robustly control system states, minimize malfunctions, and provide potential therapeutic targets in disease treatment; (iv systematic design methods for the modification and construction of biological networks with desired behaviors, which provide system design principles and system simulations for synthetic biology designs and systems metabolic engineering. This review describes current developments in systems biology, systems synthetic biology, and systems metabolic engineering for engineering and biology researchers. We also discuss challenges and future prospects for systems biology and the concept of systems biology as an integrated platform for bioinformatics, systems synthetic biology, and systems metabolic engineering.

Cascade system using both trough system and dish system for power generation

International Nuclear Information System (INIS)

Zhang, Cheng; Zhang, Yanping; Arauzo, Inmaculada; Gao, Wei; Zou, Chongzhe

2017-01-01

Highlights: • A novel solar cascade system using both trough and dish collectors is proposed. • Heat rejected by the Stirling engines is collected by the condensed water. • The directions to increase the efficiency improvement has been pointed out • Influence of flow type of heating/cooling fluids of Stirling engines is considered. - Abstract: This paper represents a novel solar thermal cascade system using both trough and dish systems for power generation. An effective structure using the condensed fluid of Rankine cycle to cool the Stirling engines to use the heat released by Stirling engines was proposed. The cascade system model with different fluid circuits was developed. The models of some important components of the system, such as dish collector, trough collector and Stirling engine array, are presented with detail explanation in this paper. Corresponding stand-alone systems were also developed for comparison. Simulations were conducted with the models to find out efficiency difference between cascade system and corresponding stand-alone systems. The directions to increase the efficiency difference were also considered. Results show that the cascade system can achieve a higher efficiency with a high solar irradiance (>550 W/m"2). The flow type of fluids between heating and cooling Stirling engine array is also required to concern on designing a cascade system with Stirling engine array.

Hybrid Propulsion Systems for Remotely Piloted Aircraft Systems

Directory of Open Access Journals (Sweden)

Mithun Abdul Sathar Eqbal

2018-03-01

Full Text Available The development of more efficient propulsion systems for aerospace vehicles is essential to achieve key objectives. These objectives are to increase efficiency while reducing the amount of carbon-based emissions. Hybrid electric propulsion (HEP is an ideal means to maintain the energy density of hydrocarbon-based fuels and utilize energy-efficient electric machines. A system that integrates different propulsion systems into a single system, with one being electric, is termed an HEP system. HEP systems have been studied previously and introduced into Land, Water, and Aerial Vehicles. This work presents research into the use of HEP systems in Remotely Piloted Aircraft Systems (RPAS. The systems discussed in this paper are Internal Combustion Engine (ICE–Electric Hybrid systems, ICE–Photovoltaic (PV Hybrid systems, and Fuel-Cell Hybrid systems. The improved performance characteristics in terms of fuel consumption and endurance are discussed.

System Budgets

DEFF Research Database (Denmark)

Jeppesen, Palle

1996-01-01

The lecture note is aimed at introducing system budgets for optical communication systems. It treats optical fiber communication systems (six generations), system design, bandwidth effects, other system impairments and optical amplifiers.......The lecture note is aimed at introducing system budgets for optical communication systems. It treats optical fiber communication systems (six generations), system design, bandwidth effects, other system impairments and optical amplifiers....

Systems Biology, Systems Medicine, Systems Pharmacology: The What and The Why.

Science.gov (United States)

Stéphanou, Angélique; Fanchon, Eric; Innominato, Pasquale F; Ballesta, Annabelle

2018-05-09

Systems biology is today such a widespread discipline that it becomes difficult to propose a clear definition of what it really is. For some, it remains restricted to the genomic field. For many, it designates the integrated approach or the corpus of computational methods employed to handle the vast amount of biological or medical data and investigate the complexity of the living. Although defining systems biology might be difficult, on the other hand its purpose is clear: systems biology, with its emerging subfields systems medicine and systems pharmacology, clearly aims at making sense of complex observations/experimental and clinical datasets to improve our understanding of diseases and their treatments without putting aside the context in which they appear and develop. In this short review, we aim to specifically focus on these new subfields with the new theoretical tools and approaches that were developed in the context of cancer. Systems pharmacology and medicine now give hope for major improvements in cancer therapy, making personalized medicine closer to reality. As we will see, the current challenge is to be able to improve the clinical practice according to the paradigm shift of systems sciences.

A contemporary view of systems engineering. [definition of system and discussion of systems approach

Science.gov (United States)

Miles, R. F., Jr.

1974-01-01

The concept of a 'system' is defined, and the 'systems approach' is discussed. Four contemporary examples of the systems approach are presented: an operations research project, the planning-programming-budgeting system, an information processing system, and aerospace programs.

A security framework for systems of systems

NARCIS (Netherlands)

Trivellato, D.; Zannone, N.; Etalle, S.

2011-01-01

Systems of systems consist of a wide variety of dynamic, distributed coalitions of autonomous and heterogeneous systems that collaborate to achieve a common goal. While offering several advantages in terms of scalability and flexibility, this new paradigm has a strong impact on system

A Security Framework for Systems of Systems

NARCIS (Netherlands)

Trivellato, Daniel; Zannone, Nicola; Etalle, Sandro

2011-01-01

Systems of systems consist of a wide variety of dynamic, distributed coalitions of autonomous and heterogeneous systems that collaborate to achieve a common goal. While offering several advantages in terms of scalability and flexibility, this new paradigm has a strong impact on system

Smart electromechanical systems the central nervous system

CERN Document Server

Kurbanov, Vugar

2017-01-01

This book describes approaches to solving the problems of developing the central nervous system of robots (CNSR) based on smart electromechanical systems (SEMS) modules, principles of construction of the various modules of the central nervous system and variants of mathematical software CNSR in control systems for intelligent robots. It presents the latest advances in theory and practice at the Russian Academy of Sciences. Developers of intelligent robots to solve modern problems in robotics are increasingly addressing the use of the bionic approach to create robots that mimic the complexity and adaptability of biological systems. These have smart electromechanical system (SEMS), which are used in various cyber-physical systems (CPhS), and allow the functions of calculation, control, communications, information storage, monitoring, measurement and control of parameters and environmental parameters to be integrated. The behavior of such systems is based on the information received from the central nervous syst...

Non linear system become linear system

Directory of Open Access Journals (Sweden)

Petre Bucur

2007-01-01

Full Text Available The present paper refers to the theory and the practice of the systems regarding non-linear systems and their applications. We aimed the integration of these systems to elaborate their response as well as to highlight some outstanding features.

Epilogue: Systems Approaches and Systems Practice

Science.gov (United States)

Reynolds, Martin; Holwell, Sue

Each of the five systems approaches discussed in this volume: system dynamics (SD), the viable systems model (VSM), strategic options development and analysis (SODA), soft systems methodology (SSM) and critical systems heuristics (CSH) has a pedigree. Not in the sense of the sometimes absurd spectacle of animals paraded at dog shows. Rather, their pedigree derives from their systems foundations, their capacity to evolve and their flexibility in use. None of the five approaches has developed out of use in restricted and controlled contexts of either low or high levels of complicatedness. Neither has any one of them evolved as a consequence of being applied only to situations with either presumed stakeholder agreement on purpose, or courteous disagreement amongst stakeholders, or stakeholder coercion. The compilation is not a celebration of abstract ‘methodologies', but of theoretically robust approaches that have a genuine pedigree in practice.

Systems theory of interconnected port contact systems

NARCIS (Netherlands)

Eberard, D.; Maschke, B.M.; Schaft, A.J. van der

2005-01-01

Port-based network modeling of a large class of complex physical systems leads to dynamical systems known as port-Hamiltonian systems. The key ingredient of any port-Hamiltonian system is a power-conserving interconnection structure (mathematically formalized by the geometric notion of a Dirac

System specifications for the NDS EXFOR System

International Nuclear Information System (INIS)

Attree, P.M.; Smith, P.M.

1979-07-01

EXFOR is the agreed exchange format for the magnetic-tape exchange of nuclear reaction data between national and international nuclear data centres for the benefit of nuclear data users in all countries. The NDS EXFOR System is a computerized system for the storage and retrieval of EXFOR information compiled or received by the IAEA. This document is an internal manual for the system specifications of the NDS EXFOR System. It includes flow charts, system and program summaries, input and output specifications and file and record descriptions. The manual is updated from time to time when system modifications are made

A Systems Thinking Approach to Engineering Challenges of Military Systems-of-Systems

Science.gov (United States)

2016-09-01

as part of organizational thinking , processes and practice; and 2) an adequate SoSE practice supporting environment created and used to enable SoS...UNCLASSIFIED UNCLLASIFIED A Systems Thinking Approach to Engineering Challenges of Military Systems-of-Systems Pin Chen and Mark...their products and outcomes. This report introduces a systems thinking -based approach, SoS thinking , which offers a language and a thoughtful process

Activity System Theory Approach to Healthcare Information System

OpenAIRE

Bai, Guohua

2004-01-01

Healthcare information system is a very complex system and has to be approached from systematic perspectives. This paper presents an Activity System Theory (ATS) approach by integrating system thinking and social psychology. First part of the paper, the activity system theory is presented, especially a recursive model of human activity system is introduced. A project ‘Integrated Mobile Information System for Diabetic Healthcare (IMIS)’ is then used to demonstrate a practical application of th...

Complex Adaptive Systems of Systems (CASOS) engineering environment.

Energy Technology Data Exchange (ETDEWEB)

Detry, Richard Joseph; Linebarger, John Michael; Finley, Patrick D.; Maffitt, S. Louise; Glass, Robert John, Jr.; Beyeler, Walter Eugene; Ames, Arlo Leroy

2012-02-01

Complex Adaptive Systems of Systems, or CASoS, are vastly complex physical-socio-technical systems which we must understand to design a secure future for the nation. The Phoenix initiative implements CASoS Engineering principles combining the bottom up Complex Systems and Complex Adaptive Systems view with the top down Systems Engineering and System-of-Systems view. CASoS Engineering theory and practice must be conducted together to develop a discipline that is grounded in reality, extends our understanding of how CASoS behave and allows us to better control the outcomes. The pull of applications (real world problems) is critical to this effort, as is the articulation of a CASoS Engineering Framework that grounds an engineering approach in the theory of complex adaptive systems of systems. Successful application of the CASoS Engineering Framework requires modeling, simulation and analysis (MS and A) capabilities and the cultivation of a CASoS Engineering Community of Practice through knowledge sharing and facilitation. The CASoS Engineering Environment, itself a complex adaptive system of systems, constitutes the two platforms that provide these capabilities.

Power Systems Integration Laboratory | Energy Systems Integration Facility

Science.gov (United States)

| NREL Power Systems Integration Laboratory Power Systems Integration Laboratory Research in the Energy System Integration Facility's Power Systems Integration Laboratory focuses on the microgrid applications. Photo of engineers testing an inverter in the Power Systems Integration Laboratory

Automatic TLI recognition system. Part 1: System description

Energy Technology Data Exchange (ETDEWEB)

Partin, J.K.; Lassahn, G.D.; Davidson, J.R.

1994-05-01

This report describes an automatic target recognition system for fast screening of large amounts of multi-sensor image data, based on low-cost parallel processors. This system uses image data fusion and gives uncertainty estimates. It is relatively low cost, compact, and transportable. The software is easily enhanced to expand the system`s capabilities, and the hardware is easily expandable to increase the system`s speed. This volume gives a general description of the ATR system.

Systems integration of business systems. Business system ni kanshite

Energy Technology Data Exchange (ETDEWEB)

Furukawa, H [Nippon Steel Corp., Tokyo (Japan)

1991-09-26

System integration (SI) is defined as combining hardwares and softwares as the infrastructures with know-hows for their use comprehensively to respond to high-level needs of users. This paper reports the features of an SI being developed by a company (E Company), its concept on the systematized development methodology, and the conceptual models. With the primary policy placed on creative integration standing on customers positions, the SI concept comprises three parts of models for evaluations as seen from the customers, evaluations as seen from the E Company, and the development object systems to link both parts. The third part is further consisted of several lower hierarchies including a customer controlled system hierarchy (this enables customers to control the system through visualization, for example, and includes three logic models (multiple solution selection, optimal solution under restricted conditions, and numerical solution)). 2 refs., 9 figs.

Fiscal system analysis - contractual systems

International Nuclear Information System (INIS)

Kaiser, M.J.

2006-01-01

Production sharing contracts are one of the most popular forms of contractual system used in petroleum agreements around the world, but the manner in which the fiscal terms and contract parameters impact system measures is complicated and not well understood. The purpose of this paper is to quantify the influence of private and market uncertainty in contractual fiscal systems. A meta-modelling approach is employed that couples the results of a simulation model with regression analysis to construct numerical functionals that quantify the fiscal regime. Relationships are derived that specify how the present value, rate of return, and take statistics vary as a function of the system parameters. The deepwater Girassol field development in Angola is taken as a case study. (author)

System Entropy Measurement of Stochastic Partial Differential Systems

Directory of Open Access Journals (Sweden)

Bor-Sen Chen

2016-03-01

Full Text Available System entropy describes the dispersal of a system’s energy and is an indication of the disorder of a physical system. Several system entropy measurement methods have been developed for dynamic systems. However, most real physical systems are always modeled using stochastic partial differential dynamic equations in the spatio-temporal domain. No efficient method currently exists that can calculate the system entropy of stochastic partial differential systems (SPDSs in consideration of the effects of intrinsic random fluctuation and compartment diffusion. In this study, a novel indirect measurement method is proposed for calculating of system entropy of SPDSs using a Hamilton–Jacobi integral inequality (HJII-constrained optimization method. In other words, we solve a nonlinear HJII-constrained optimization problem for measuring the system entropy of nonlinear stochastic partial differential systems (NSPDSs. To simplify the system entropy measurement of NSPDSs, the global linearization technique and finite difference scheme were employed to approximate the nonlinear stochastic spatial state space system. This allows the nonlinear HJII-constrained optimization problem for the system entropy measurement to be transformed to an equivalent linear matrix inequalities (LMIs-constrained optimization problem, which can be easily solved using the MATLAB LMI-toolbox (MATLAB R2014a, version 8.3. Finally, several examples are presented to illustrate the system entropy measurement of SPDSs.

System specifications for the NDS EXFOR System

Energy Technology Data Exchange (ETDEWEB)

Attree, P M; Smith, P M

1982-06-01

EXFOR is the agreed exchange format for the magnetic-tape exchange of nuclear reaction data between national and international nuclear data centers for the benefit of nuclear data users in all countries. The NDS EXFOR System is a computerized system for the storage and retrieval of EXFOR information compiled or received of the IAEA. This document is an internal manual for the system specifications of the NDS EXFOR System. It includes flow charts, system and program summaries, input and output specifications and file and record descriptions. The manual is updated from time to time when system modifications are made; the first version was issued in July 1979. (author)

Performance of integrated systems of automated roller shade systems and daylight responsive dimming systems

Energy Technology Data Exchange (ETDEWEB)

Park, Byoung-Chul; Choi, An-Seop; Jeong, Jae-Weon [Department of Architectural Engineering, Sejong University, Kunja-Dong, Kwangjin-Gu, Seoul (Korea, Republic of); Lee, Eleanor S. [Building Technologies Department, Lawrence Berkeley National Laboratory, Berkeley, CA (United States)

2011-03-15

Daylight responsive dimming systems have been used in few buildings to date because they require improvements to improve reliability. The key underlying factor contributing to poor performance is the variability of the ratio of the photosensor signal to daylight workplane illuminance in accordance with sun position, sky condition, and fenestration condition. Therefore, this paper describes the integrated systems between automated roller shade systems and daylight responsive dimming systems with an improved closed-loop proportional control algorithm, and the relative performance of the integrated systems and single systems. The concept of the improved closed-loop proportional control algorithm for the integrated systems is to predict the varying correlation of photosensor signal to daylight workplane illuminance according to roller shade height and sky conditions for improvement of the system accuracy. In this study, the performance of the integrated systems with two improved closed-loop proportional control algorithms was compared with that of the current (modified) closed-loop proportional control algorithm. In the results, the average maintenance percentage and the average discrepancies of the target illuminance, as well as the average time under 90% of target illuminance for the integrated systems significantly improved in comparison with the current closed-loop proportional control algorithm for daylight responsive dimming systems as a single system. (author)

Reliability-Based Optimization of Series Systems of Parallel Systems

DEFF Research Database (Denmark)

Enevoldsen, I.; Sørensen, John Dalsgaard

1993-01-01

Reliability-based design of structural systems is considered. In particular, systems where the reliability model is a series system of parallel systems are treated. A sensitivity analysis for this class of problems is presented. Optimization problems with series systems of parallel systems...... optimization of series systems of parallel systems, but it is also efficient in reliability-based optimization of series systems in general....

Cobit system in the audit processes of the systems of computer systems

Directory of Open Access Journals (Sweden)

Julio Jhovany Santacruz Espinoza

2017-12-01

Full Text Available The present research work has been carried out to show the benefits of the use of the COBIT system in the auditing processes of the computer systems, the problem is related to: How does it affect the process of audits in the institutions, use of the COBIT system? The main objective is to identify the incidence of the use of the COBIT system in the auditing process used by computer systems within both public and private organizations; In order to achieve our stated objectives of the research will be developed first with the conceptualization of key terms for an easy understanding of the subject, as a conclusion: we can say the COBIT system allows to identify the methodology by using information from the IT departments, to determine the resources of the (IT Information Technology, specified in the COBIT system, such as files, programs, computer networks, including personnel that use or manipulate the information, with the purpose of providing information that the organization or company requires to achieve its objectives.

Chaos synchronization between Chen system and Genesio system

International Nuclear Information System (INIS)

Wu Xianyong; Guan Zhihong; Wu Zhengping; Li Tao

2007-01-01

This Letter presents two synchronization schemes between two different chaotic systems. Active control synchronization and adaptive synchronization between Chen system and Genesio system are studied, different controllers are designed to synchronize the drive and response systems, active control synchronization is used when system parameters are known; adaptive synchronization is employed when system parameters are unknown or uncertain. Simulation results show the effectiveness of the proposed schemes

Embedded systems design with special arithmetic and number systems

CERN Document Server

Sousa, Leonel; Chang, Chip-Hong

2017-01-01

This book introduces readers to alternative approaches to designing efficient embedded systems using unconventional number systems. The authors describe various systems that can be used for designing efficient embedded and application-specific processors, such as Residue Number System, Logarithmic Number System, Redundant Binary Number System Double-Base Number System, Decimal Floating Point Number System and Continuous Valued Number System. Readers will learn the strategies and trade-offs of using unconventional number systems in application-specific processors and be able to apply and design appropriate arithmetic operations from these number systems to boost the performance of digital systems. • Serves as a single-source reference to designing embedded systems with unconventional number systems • Covers theory as well as implementation on application-specific processors • Explains mathematical concepts in a manner accessible to readers with diverse backgrounds.

Expert systems in process control systems

International Nuclear Information System (INIS)

Wittig, T.

1987-01-01

To illustrate where the fundamental difference between expert systems in classical diagnosis and in industrial control lie, the work of process control instrumentation is used as an example for the job of expert systems. Starting from the general process of problem-solving, two classes of expert systems can be defined accordingly. (orig.) [de

Amotosalen: Allogeneic Cellular Immunotherapies system, INTERCEPT Plasma System, INTERCEPT Platelet System, S 59.

Science.gov (United States)

2003-01-01

Adis CommentsCerus Corporation is developing a variety of pathogen-inactivation systems, based on its Helinx technology. Three of the systems include amotosalen [S 59] as the inactivation compound. Amotosalen is a light-activated, DNA-, RNA-crosslinking psoralen compound, which is used to neutralise pathogens. The systems that utilise amotosalen are called the INTERCEPT Platelet System, the INTERCEPT Plasma System and the Allogeneic Cellular Immunotherapies (ACIT) system. The INTERCEPT Platelet System and INTERCEPT Plasma System are two of the systems that make up Cerus' INTERCEPT Blood Systems. The other system is the INTERCEPT Red Blood Cell System, which contains S 303 as the inactivation compound rather than amotosalen. Cerus' Helinx technology is able to prevent replication of DNA or RNA that is present in pathogens but not in the blood components being treated (e.g. platelets and plasma). When added to the blood components, the inactivation agent (in this case amotosalen) crosses the membrane or cell wall of the pathogen. When activated by light, amotosalen binds to the nucleic acid of the pathogen and prevents replication. This process prevents infection. INTERCEPT Platelet System: Cerus developed its INTERCEPT Platelet System, in collaboration with Baxter Healthcare, for use in blood centres. Platelets are an essential component of the coagulation process and may be required by patients undergoing surgery, cancer chemotherapy, transplantation or with bleeding disorders. The system is made up of an illuminator device, a compound absorption device and a processing kit containing amotosalen. In October 2002, the two companies announced that CE Mark approval had been received for the illuminator device for the INTERCEPT trade mark Blood System. Application of this technology to platelets is the first to be approved. As it is a new technology, the system is currently undergoing process validation in accordance with European Blood Bank GMP requirements. This

Manager's assistant systems for space system planning

Science.gov (United States)

Bewley, William L.; Burnard, Robert; Edwards, Gary E.; Shoop, James

1992-01-01

This paper describes a class of knowledge-based 'assistant' systems for space system planning. Derived from technology produced for the DARPA/USAF Pilot's Associate program, these assistant systems help the human planner by doing the bookkeeping to maintain plan data and executing the procedures and heuristics currently used by the human planner to define, assess, diagnose, and revise plans. Intelligent systems for Space Station Freedom assembly sequence planning and Advanced Launch System modeling will be presented as examples. Ongoing NASA-funded work on a framework supporting the development of such tools will also be described.

Systems of Systems: Scaling Up the Development Process

National Research Council Canada - National Science Library

Humphrey, Watts

2006-01-01

... of massive systems into system-of-systems structures Section 3 points out how large-scale systems development efforts have typically failed because of project-management and not technical problems...

Digital processing data communication systems (bus systems)

International Nuclear Information System (INIS)

Fleck, K.

1980-01-01

After an introduction to the technology of digital processing data communication systems there are the following chapters: digital communication of processing data in automation technology, the technology of biserial communication, the implementaiton of a bus system, the data transmission of the TDC-2000 system of Honeywell's and the process bus CS 275 in the automation system TELEPERM M of Siemens AG. (WB) [de

System-of-Systems Approach for Integrated Energy Systems Modeling and Simulation: Preprint

Energy Technology Data Exchange (ETDEWEB)

Mittal, Saurabh; Ruth, Mark; Pratt, Annabelle; Lunacek, Monte; Krishnamurthy, Dheepak; Jones, Wesley

2015-08-21

Today’s electricity grid is the most complex system ever built—and the future grid is likely to be even more complex because it will incorporate distributed energy resources (DERs) such as wind, solar, and various other sources of generation and energy storage. The complexity is further augmented by the possible evolution to new retail market structures that provide incentives to owners of DERs to support the grid. To understand and test new retail market structures and technologies such as DERs, demand-response equipment, and energy management systems while providing reliable electricity to all customers, an Integrated Energy System Model (IESM) is being developed at NREL. The IESM is composed of a power flow simulator (GridLAB-D), home energy management systems implemented using GAMS/Pyomo, a market layer, and hardware-in-the-loop simulation (testing appliances such as HVAC, dishwasher, etc.). The IESM is a system-of-systems (SoS) simulator wherein the constituent systems are brought together in a virtual testbed. We will describe an SoS approach for developing a distributed simulation environment. We will elaborate on the methodology and the control mechanisms used in the co-simulation illustrated by a case study.

Linear Actuator System for the NASA Docking System

Science.gov (United States)

Dick, Brandon N.; Oesch, Christopher; Rupp, Timothy W.

2017-01-01

The Linear Actuator System (LAS) is a major sub-system within the NASA Docking System (NDS). The NDS Block 1 will be used on the Boeing Crew Space Transportation (CST-100) system to achieve docking with the International Space Station. Critical functions in the Soft Capture aspect of docking are performed by the LAS. This paper describes the general function of the LAS, the system's key requirements and technical challenges, and the development and qualification approach for the system.

Methods, apparatus, and systems for monitoring transmission systems

Science.gov (United States)

Polk, Robert E [Idaho Falls, ID; Svoboda, John M [Idaho Falls, ID; West, Phillip B [Idaho Falls, ID; Heath, Gail L [Iona, ID; Scott, Clark L [Idaho Falls, ID

2010-08-31

A sensing platform for monitoring a transmission system, and method therefor, may include a sensor that senses one or more conditions relating to a condition of the transmission system and/or the condition of an environment around the transmission system. A control system operatively associated with the sensor produces output data based on an output signal produced by the sensor. A transmitter operatively associated with the control system transmits the output data from the control system.

System Engineering of Photonic Systems for Space Application

Science.gov (United States)

Watson, Michael D.; Pryor, Jonathan E.

2014-01-01

The application of photonics in space systems requires tight integration with the spacecraft systems to ensure accurate operation. This requires some detailed and specific system engineering to properly incorporate the photonics into the spacecraft architecture and to guide the spacecraft architecture in supporting the photonics devices. Recent research in product focused, elegant system engineering has led to a system approach which provides a robust approach to this integration. Focusing on the mission application and the integration of the spacecraft system physics incorporation of the photonics can be efficiently and effectively accomplished. This requires a clear understanding of the driving physics properties of the photonics device to ensure proper integration with no unintended consequences. The driving physics considerations in terms of optical performance will be identified for their use in system integration. Keywords: System Engineering, Optical Transfer Function, Optical Physics, Photonics, Image Jitter, Launch Vehicle, System Integration, Organizational Interaction

Systems

International Nuclear Information System (INIS)

Anon.

1980-01-01

Papers in this session describe the concept of mined geologic disposal system and methods for ensuring that the system, when developed, will meet all technical requirements. Also presented in the session are analyses of system parameters, such as cost and nuclear criticality potential, as well as a technical analysis of a requirement that the system permit retrieval of the waste for some period of time. The final paper discusses studies under way to investigate technical alternatives or complements to the mined geologic disposal system. Titles of the presented papers are: (1) Waste Isolation System; (2) Waste Isolation Economics; (3) BWIP Technical Baseline; (4) Criticality Considerations in Geologic Disposal of High-Level Waste; (5) Retrieving Nuclear Wastes from Repository; (6) NWTS Programs for the Evaluation of Technical Alternatives or Complements to Mined Geologic Repositories - Purpose and Objectives

systems

Directory of Open Access Journals (Sweden)

Alexander Leonessa

2000-01-01

Full Text Available A nonlinear robust control-system design framework predicated on a hierarchical switching controller architecture parameterized over a set of moving nominal system equilibria is developed. Specifically, using equilibria-dependent Lyapunov functions, a hierarchical nonlinear robust control strategy is developed that robustly stabilizes a given nonlinear system over a prescribed range of system uncertainty by robustly stabilizing a collection of nonlinear controlled uncertain subsystems. The robust switching nonlinear controller architecture is designed based on a generalized (lower semicontinuous Lyapunov function obtained by minimizing a potential function over a given switching set induced by the parameterized nominal system equilibria. The proposed framework robustly stabilizes a compact positively invariant set of a given nonlinear uncertain dynamical system with structured parametric uncertainty. Finally, the efficacy of the proposed approach is demonstrated on a jet engine propulsion control problem with uncertain pressure-flow map data.

Üniversite Öğrencilerinde Okul Tükenmişliği ile Psikolojik Uyumsuzluk Arasındaki İlişkinin İncelenmesi

OpenAIRE

Seçer, İsmail

2015-01-01

The purpose of this study is to analyze the relation between the school burnout and psychological disorder (depression, anxiety and stress) of the university students. The study is a correlational research and a descriptive research. Correlational research is a research which aims to determine whether there is and/or what level is a common change in two or more variables. Maslach Burnout Inventory- Student Form and Depression Anxiety Stress Scale was applied on the sample of the study which w...

Ergenlerde Mobil Telefon Bağımlığı İle Sosyal Kaygı Arasındaki İlişkinin İncelenmesi

OpenAIRE

YILMAZ, Gül; ŞAR, Ali Haydar; CİVAN, Sema

2015-01-01

Araştırmanın amacı mobil telefon bağımlılığının ergenlerin sosyal kaygı düzeyleri üzerindeki işleyişlerini incelemektir. Sosyal kaygı düzeyleri incelenirken gittikçe artan ve hayatımızın her anını saran telefon kullanımlarının ergenler üzerindeki sosyal kaygı derecesini ve bunların yaş, cinsiyet, eğitim gibi faktörlere bağlı olarak nasıl değişkenlik gösterdiği araştırılmıştır.Araştırma da öncelikle sosyal kaygı kavramının gelişimine ve aşamalarına bakılmış ardından ergenlik dönemlerinin özell...

Ventilation systems

International Nuclear Information System (INIS)

Gossler

1980-01-01

The present paper deals with - controlled area ventilation systems - ventilation systems for switchgear-building and control-room - other ventilation systems for safety equipments - service systems for ventilation systems. (orig./RW)

SSDL personel dosimetry system: migration from a client - server system into a web-based system

International Nuclear Information System (INIS)

Maizura Ibrahim; Rosnah Shariff; Ahmad Bazlie Abdul Kadir; John Konsoh Sangau; Mohd Amin Sharifuldin Salleh; Taiman Kadni; Noriah Mod Ali

2007-01-01

Personnel Dosimetry System has been used by the Secondary Standard Dosimetry Laboratory (SSDL), Nuclear Malaysia since ten years ago. The system is a computerized database system with a client-server concept. This system has been used by Film Badge Laboratory, SSDL to record details of clients, calculation of Film Badge dosage, management of radiation workers data's, generating of dosage report, retrieval of statistical reports regarding film badge usage for the purpose of reporting to monitoring bodies such as Atomic Energy Licensing Board (AELB), Ministry of Health and others. But, due to technical problems that frequently occurs, the system is going to be replaced by a newly developed web- based system called e-SSDL. This paper describe the problems that regularly occurs in the previous system, explains how the process of replacing the client-server system with a web-based system is done and the differences between the previous and current system. This paper will also present details architecture of the new system and the new process introduced in processing film badges. (Author)

Real-Time Operating Systems for Multicore Embedded Systems

OpenAIRE

Tomiyama, Hiroyuki; Honda, Shinya; Takada, Hiroaki

2008-01-01

Multicore systems-on-chip have become popular inthe design of embedded systems in order to simultaneously achieve high performance and low power consumption. On the software side, real-time operating systems are necessary in orderto handle growing complexity of embedded software. This paper describes requirements, design principles and implementation techniques for real-time operating systems to be used inasymmetric multicore systems.

EXPERT SYSTEMS

OpenAIRE

Georgiana Marin; Mihai Catalin Andrei

2011-01-01

In recent decades IT and computer systems have evolved rapidly in economic informatics field. The goal is to create user friendly information systems that respond promptly and accurately to requests. Informatics systems evolved into decision assisted systems, and such systems are converted, based on gained experience, in expert systems for creative problem solving that an organization is facing. Expert systems are aimed at rebuilding human reasoning on the expertise obtained from experts, sto...

A master system for power system fault phenomena

Energy Technology Data Exchange (ETDEWEB)

Yoo, Myung Ho; Jang, Sang Ho; Hong, Joon Hee; Min, Wan Ki; Yoo, Chang Hwan [Korea Electric Power Corp. (KEPCO), Taejon (Korea, Republic of). Research Center

1995-12-31

This report includes as follows - Real time digital simulator - Remote measuring, analyzing and reproducing system of power system fault data -Power system reduction method program using EMTP -Test system for protection device. (author). 22 refs., 38 figs.

T-systems and Y-systems in integrable systems

International Nuclear Information System (INIS)

Kuniba, Atsuo; Nakanishi, Tomoki; Suzuki, Junji

2011-01-01

T- and Y-systems are ubiquitous structures in classical and quantum integrable systems. They are difference equations having a variety of aspects related to commuting transfer matrices in solvable lattice models, q-characters of Kirillov-Reshetikhin modules of quantum affine algebras, cluster algebras with coefficients, periodicity conjectures of Zamolodchikov and others, dilogarithm identities in conformal field theory, difference analog of L-operators in KP hierarchy, Stokes phenomena in 1D Schroedinger problem, AdS/CFT correspondence, Toda field equations on discrete spacetime, Laplace sequence in discrete geometry, Fermionic character formulas and combinatorial completeness of Bethe ansatz, Q-system and ideal gas with exclusion statistics, analytic and thermodynamic Bethe ansaetze, quantum transfer matrix method and so forth. This review is a collection of short reviews on these topics which can be read more or less independently. (topical review)

T-systems and Y-systems in integrable systems

Energy Technology Data Exchange (ETDEWEB)

Kuniba, Atsuo [Institute of Physics, University of Tokyo, Komaba, Tokyo 153-8902 (Japan); Nakanishi, Tomoki [Graduate School of Mathematics, Nagoya University, Nagoya 464-8604 (Japan); Suzuki, Junji, E-mail: atsuo@gokutan.c.u-tokyo.ac.jp [Department of Physics, Faculty of Science, Shizuoka University, Ohya 836 (Japan)

2011-03-11

T- and Y-systems are ubiquitous structures in classical and quantum integrable systems. They are difference equations having a variety of aspects related to commuting transfer matrices in solvable lattice models, q-characters of Kirillov-Reshetikhin modules of quantum affine algebras, cluster algebras with coefficients, periodicity conjectures of Zamolodchikov and others, dilogarithm identities in conformal field theory, difference analog of L-operators in KP hierarchy, Stokes phenomena in 1D Schroedinger problem, AdS/CFT correspondence, Toda field equations on discrete spacetime, Laplace sequence in discrete geometry, Fermionic character formulas and combinatorial completeness of Bethe ansatz, Q-system and ideal gas with exclusion statistics, analytic and thermodynamic Bethe ansaetze, quantum transfer matrix method and so forth. This review is a collection of short reviews on these topics which can be read more or less independently. (topical review)

Sail GTS ground system analysis: Avionics system engineering

Science.gov (United States)

Lawton, R. M.

1977-01-01

A comparison of two different concepts for the guidance, navigation and control test set signal ground system is presented. The first is a concept utilizing a ground plate to which crew station, avionics racks, electrical power distribution system, master electrical common connection assembly and marshall mated elements system grounds are connected by 4/0 welding cable. An alternate approach has an aluminum sheet interconnecting the signal ground reference points between the crew station and avionics racks. The comparison analysis quantifies the differences between the two concepts in terms of dc resistance, ac resistance and inductive reactance. These parameters are figures of merit for ground system conductors in that the system with the lowest impedance is the most effective in minimizing noise voltage. Although the welding cable system is probably adequate, the aluminum sheet system provides a higher probability of a successful system design.

Multiple Energy System Analysis of Smart Energy Systems

DEFF Research Database (Denmark)

Thellufsen, Jakob Zinck

2015-01-01

thermal grids and smart gas grids, Smart Energy Systems moves the flexibility away from the fuel as is the case in current energy systems and into the system itself. However, most studies applying a Smart Energy System approach deals with analyses for either single countries or whole continents......To eliminate the use of fossil fuels in the energy sector it is necessary to transition to future 100% renewable energy systems. One approach for this radical change in our energy systems is Smart Energy Systems. With a focus on development and interaction between smart electricity grids, smart......, but it is unclear how regions, municipalities, and communities should deal with these national targets. It is necessary to be able to provide this information since Smart Energy Systems utilize energy resources and initiatives that have strong relations to local authorities and communities, such as onshore wind...

Cooling system for the IFMIF-EVEDA radiofrequency system

International Nuclear Information System (INIS)

Perez Pichel, G. D.

2012-01-01

The IFMIF-EVEDA project consists on an accelerator prototype that will be installed at Rokkasho (Japan). Through CIEMAT, that is responsible of the development of many systems and components. Empresarios Agrupados get the responsibility of the detailed design of the cooling system for the radiofrequency system (RF system) that must feed the accelerator. the RF water cooling systems is the water primary circuit that provides the required water flow (with a certain temperature, pressure and water quality) and also dissipates the necessary thermal power of all the radiofrequency system equipment. (Author) 4 refs.

Tritium system test assembly control system cost estimate

International Nuclear Information System (INIS)

Stutz, R.A.

1979-01-01

The principal objectives of the Tritium Systems Test Assembly (TSTA), which includes the development, demonstration and interfacing of technologies related to the deuterium--tritium fuel cycle for fusion reactor systems, are concisely stated. The various integrated subsystems comprising TSTA and their functions are discussed. Each of the four major subdivisions of TSTA, including the main process system, the environmental and safety systems, supporting systems and the physical plant are briefly discussed. An overview of the Master Data Acquisition and Control System, which will control all functional operation of TSTA, is provided

Site systems engineering: Systems engineering management plan

Energy Technology Data Exchange (ETDEWEB)

Grygiel, M.L. [Westinghouse Hanford Co., Richland, WA (United States)

1996-05-03

The Site Systems Engineering Management Plan (SEMP) is the Westinghouse Hanford Company (WHC) implementation document for the Hanford Site Systems Engineering Policy, (RLPD 430.1) and Systems Engineering Criteria Document and Implementing Directive, (RLID 430.1). These documents define the US Department of Energy (DOE), Richland Operations Office (RL) processes and products to be used at Hanford to implement the systems engineering process at the site level. This SEMP describes the products being provided by the site systems engineering activity in fiscal year (FY) 1996 and the associated schedule. It also includes the procedural approach being taken by the site level systems engineering activity in the development of these products and the intended uses for the products in the integrated planning process in response to the DOE policy and implementing directives. The scope of the systems engineering process is to define a set of activities and products to be used at the site level during FY 1996 or until the successful Project Hanford Management Contractor (PHMC) is onsite as a result of contract award from Request For Proposal DE-RP06-96RL13200. Following installation of the new contractor, a long-term set of systems engineering procedures and products will be defined for management of the Hanford Project. The extent to which each project applies the systems engineering process and the specific tools used are determined by the project`s management.

System safety education focused on system management

Science.gov (United States)

Grose, V. L.

1971-01-01

System safety is defined and characteristics of the system are outlined. Some of the principle characteristics include role of humans in hazard analysis, clear language for input and output, system interdependence, self containment, and parallel analysis of elements.

Modeling Power Systems as Complex Adaptive Systems

Energy Technology Data Exchange (ETDEWEB)

Chassin, David P.; Malard, Joel M.; Posse, Christian; Gangopadhyaya, Asim; Lu, Ning; Katipamula, Srinivas; Mallow, J V.

2004-12-30

Physical analogs have shown considerable promise for understanding the behavior of complex adaptive systems, including macroeconomics, biological systems, social networks, and electric power markets. Many of today's most challenging technical and policy questions can be reduced to a distributed economic control problem. Indeed, economically based control of large-scale systems is founded on the conjecture that the price-based regulation (e.g., auctions, markets) results in an optimal allocation of resources and emergent optimal system control. This report explores the state-of-the-art physical analogs for understanding the behavior of some econophysical systems and deriving stable and robust control strategies for using them. We review and discuss applications of some analytic methods based on a thermodynamic metaphor, according to which the interplay between system entropy and conservation laws gives rise to intuitive and governing global properties of complex systems that cannot be otherwise understood. We apply these methods to the question of how power markets can be expected to behave under a variety of conditions.

Integrated Systems Health Management for Intelligent Systems

Science.gov (United States)

Figueroa, Fernando; Melcher, Kevin

2011-01-01

The implementation of an integrated system health management (ISHM) capability is fundamentally linked to the management of data, information, and knowledge (DIaK) with the purposeful objective of determining the health of a system. It is akin to having a team of experts who are all individually and collectively observing and analyzing a complex system, and communicating effectively with each other in order to arrive at an accurate and reliable assessment of its health. In this paper, concepts, procedures, and approaches are presented as a foundation for implementing an intelligent systems ]relevant ISHM capability. The capability stresses integration of DIaK from all elements of a system. Both ground-based (remote) and on-board ISHM capabilities are compared and contrasted. The information presented is the result of many years of research, development, and maturation of technologies, and of prototype implementations in operational systems.

Systems Measures of Water Distribution System Resilience

Energy Technology Data Exchange (ETDEWEB)

Klise, Katherine A. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Murray, Regan [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Walker, La Tonya Nicole [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

2015-01-01

Resilience is a concept that is being used increasingly to refer to the capacity of infrastructure systems to be prepared for and able to respond effectively and rapidly to hazardous events. In Section 2 of this report, drinking water hazards, resilience literature, and available resilience tools are presented. Broader definitions, attributes and methods for measuring resilience are presented in Section 3. In Section 4, quantitative systems performance measures for water distribution systems are presented. Finally, in Section 5, the performance measures and their relevance to measuring the resilience of water systems to hazards is discussed along with needed improvements to water distribution system modeling tools.

Instrument air system - Aging impact on system availability

International Nuclear Information System (INIS)

Villaran, M.; Subudhi, M.

1989-01-01

As part of ongoing efforts to understand and manage the effects of aging in nuclear power plants, an aging assessment was performed for the Instrument Air (IA) system, a system that has been the subject of much scrutiny in recent years. Despite its non-safety classification, instrument air has been a factor in a number of potentially serious events. This report presents the results of the assessment and discusses the impact of instrument air system aging on system availability and plant safety. This work was performed for the US Nuclear Regulatory Commission (NRC) as part of the Nuclear Plant Aging Research (NPAR) program. To perform the complex task of analyzing an entire system, the Aging and Life Extension Assessment Program (ALEAP) System Level Plan was developed by Brookhaven National Laboratory and applied successfully in previous system aging studies. The work presented herein was performed using two parallel work paths, as described in the ALEAP plant. One path used deterministic techniques to assess the impact of aging on compressed air system performance, while the second path used probabilistic methods. Results from both paths then were used to characterize aging in the instrument air system. Some conclusions from this work are: compressors, air system valves, and air dryers were found to make up the majority of failures; the effectiveness and quantity of preventive maintenance devoted to a component significantly affected the amount of failures experienced; review of compressed air system designs and studies using a PRA-based system model revealed that the redundancy of key components (compressors, dryers, IA/SA crossconnect valve) was an important factor in system availability; total loss of air events are uncommon

Airport Information Retrieval System (AIRS) System Design

Science.gov (United States)

1974-07-01

This report presents the system design for a prototype air traffic flow control automation system developed for the FAA's Systems Command Center. The design was directed toward the immediate automation of airport data for use in traffic load predicti...

System description of the Basic MRS System for the FY 1990 Systems Integration Program studies

International Nuclear Information System (INIS)

McKee, R.W.; Young, J.R.; Konzek, G.J.

1991-07-01

This document provides both functional and physical descriptions of a conceptual high-level waste management system defined as a Basic MRS System. Its purpose is to provide a basis for required system computer modeling and system studies initiated in FY 1990 under the Systems Integration Program of the Office of Civilian Radioactive Waste Management Office (OCRWM). Two specific systems studies initiated in FY 1990, the Reference System Performance Evaluation and the Aggregate Receipt Rate Study, utilize the information in this document. The Basic MRS System is the current OCRWM reference high-level radioactive wastes repository system concept. It is designed to accept 3000 MTU per year of spent fuel and 400 equivalent MTU per year of high-level wastes. The Basic MRS System includes a storage-only MRS that provides for a limited amount of commercial spent fuel storage capacity prior to acceptance by the geologic repository for disposal. This document contains both functional descriptions of the processes in the waste management system and physical descriptions of the equipment and facilities necessary for performance of those processes. The basic MRS system contains all system components, from the waste storage facilities of the waste generators to the underground facilities for final disposal of the wastes. The major facilities in the system are the waste generator waste storage facilities, an MRS facility that provides interim storage wastes accepted from the waste generators, a repository facility that packages the wastes and then emplaces them in the geologic repository, and the transportation equipment and facilities for transporting the waste between these major facilities

Systems Biology and Health Systems Complexity in;

NARCIS (Netherlands)

Donald Combs, C.; Barham, S.R.; Sloot, P.M.A.

2016-01-01

Systems biology addresses interactions in biological systems at different scales of biological organization, from the molecular to the cellular, organ, organism, societal, and ecosystem levels. This chapter expands on the concept of systems biology, explores its implications for individual patients

Triggering system innovation in agricultural innovation systems

NARCIS (Netherlands)

Turner, James A.; Williams, Tracy; Nicholas, Graeme; Foote, Jeff; Rijswijk, Kelly; Barnard, Tim; Beechener, Sam; Horita, Akiko

2017-01-01

This article describes a process for stimulating engagement among change agents to develop a shared understanding of systemic problems in the agricultural innovation system (AIS), challenge prevalent institutional logics and identify actions they might undertake to stimulate system innovation.

Port contact systems for irreversible thermodynamical systems

NARCIS (Netherlands)

Eberard, D.; Maschke, B.M.; Schaft, A.J. van der

2005-01-01

In this paper we propose a definition of control contact systems, generalizing input-output Hamiltonian systems, to cope with models arising from irreversible Thermodynamics. We exhibit a particular subclass of these systems, called conservative, that leaves invariant some Legendre submanifold (the

Lectures on algebraic system theory: Linear systems over rings

Science.gov (United States)

Kamen, E. W.

1978-01-01

The presentation centers on four classes of systems that can be treated as linear systems over a ring. These are: (1) discrete-time systems over a ring of scalars such as the integers; (2) continuous-time systems containing time delays; (3) large-scale discrete-time systems; and (4) time-varying discrete-time systems.

IDAPS (Image Data Automated Processing System) System Description

Science.gov (United States)

1988-06-24

This document describes the physical configuration and components used in the image processing system referred to as IDAPS (Image Data Automated ... Processing System). This system was developed by the Environmental Research Institute of Michigan (ERIM) for Eglin Air Force Base. The system is designed

A semantic security framework for systems of systems

NARCIS (Netherlands)

Trivellato, Daniel; Zannone, Nicola; Glaundrup, Maurice; Skowronek, Jacek; Etalle, Sandro

2013-01-01

Systems of systems (SoS) are dynamic coalitions of distributed, autonomous and heterogeneous systems that collaborate to achieve a common goal. While offering several advantages in terms of scalability and flexibility, the SoS paradigm has a strong impact on systems interoperability and on the

Thermal Distribution System | Energy Systems Integration Facility | NREL

Science.gov (United States)

Thermal Distribution System Thermal Distribution System The Energy Systems Integration Facility's . Photo of the roof of the Energy Systems Integration Facility. The thermal distribution bus allows low as 10% of its full load level). The 60-ton chiller cools water with continuous thermal control

Seamless integrated network system for wireless communication systems

NARCIS (Netherlands)

Wu, Gang; Mizuno, Mitsuhiko; Hase, Yoshihiro; Havinga, Paul J.M.

2006-01-01

To create a network that connects a plurality of wireless communication systems to create optimal systems for various environments, and that seamlessly integrates the resulting systems together in order to provide more efficient and advanced service in general. A network system that can seamlessly

Seamless integrated network system for wireless communication systems

NARCIS (Netherlands)

Wu, Gang; Mizuno, Mitsuhiko; Hase, Yoshihiro; Havinga, Paul J.M.

2002-01-01

To create a network that connects a plurality of wireless communication systems to create optimal systems for various environments, and that seamlessly integrates the resulting systems together in order to provide more efficient and advanced service in general. A network system that can seamlessly

Modeling learning technology systems as business systems

NARCIS (Netherlands)

Avgeriou, Paris; Retalis, Symeon; Papaspyrou, Nikolaos

2003-01-01

The design of Learning Technology Systems, and the Software Systems that support them, is largely conducted on an intuitive, ad hoc basis, thus resulting in inefficient systems that defectively support the learning process. There is now justifiable, increasing effort in formalizing the engineering

Database management system for large container inspection system

International Nuclear Information System (INIS)

Gao Wenhuan; Li Zheng; Kang Kejun; Song Binshan; Liu Fang

1998-01-01

Large Container Inspection System (LCIS) based on radiation imaging technology is a powerful tool for the Customs to check the contents inside a large container without opening it. The author has discussed a database application system, as a part of Signal and Image System (SIS), for the LCIS. The basic requirements analysis was done first. Then the selections of computer hardware, operating system, and database management system were made according to the technology and market products circumstance. Based on the above considerations, a database application system with central management and distributed operation features has been implemented

Verification and Validation Issues in Systems of Systems

Directory of Open Access Journals (Sweden)

Eric Honour

2013-11-01

Full Text Available The cutting edge in systems development today is in the area of "systems of systems" (SoS large networks of inter-related systems that are developed and managed separately, but that also perform collective activities. Such large systems typically involve constituent systems operating with different life cycles, often with uncoordinated evolution. The result is an ever-changing SoS in which adaptation and evolution replace the older engineering paradigm of "development". This short paper presents key thoughts about verification and validation in this environment. Classic verification and validation methods rely on having (a a basis of proof, in requirements and in operational scenarios, and (b a known system configuration to be proven. However, with constant SoS evolution, management of both requirements and system configurations are problematic. Often, it is impossible to maintain a valid set of requirements for the SoS due to the ongoing changes in the constituent systems. Frequently, it is even difficult to maintain a vision of the SoS operational use as users find new ways to adapt the SoS. These features of the SoS result in significant challenges for system proof. In addition to discussing the issues, the paper also indicates some of the solutions that are currently used to prove the SoS.

Systems Theory and Systems Approach to Leadership

Directory of Open Access Journals (Sweden)

Dr.Sc. Berim Ramosaj

2014-06-01

Full Text Available Systems theory is product of the efforts of many researchers to create an intermediate field of coexistence of all sciences. If not for anything else, because of the magnitude that the use of systemic thinking and systemic approach has taken, it has become undisputed among the theories. Systems theory not only provides a glossary of terms with which researchers from different fields can be understood, but provides a framework for the presentation and interpretation of phenomena and realities. This paper addresses a systematic approach to leadership, as an attempt to dredge leadership and systems theory literature to find the meeting point. Systems approach is not an approach to leadership in terms of a manner of leader’s work, but it’s the leader's determination to factorize in his leadership the external environment and relationships with and among elements. Leader without followers is unable to exercise his leadership and to ensure their conviction he should provide a system, a structure, a purpose, despite the alternative chaos. Systems approach clarifies the thought on the complexity and dynamism of the environment and provides a framework for building ideas. If the general system theory is the skeleton of science (Boulding: 1956, this article aims to replenish it with leadership muscles by prominent authors who have written on systems theory and leadership, as well as through original ideas. In this work analytical methods were used (by analyzing approaches individually as well as synthetic methods (by assaying individual approaches in context of entirety. The work is a critical review of literature as well as a deductive analysis mingled with models proposed by authors through inductive analysis. Meta-analysis has been used to dissect the interaction and interdependence between leadership approaches.

Peripheral Nervous System Manifestations in Systemic Autoimmune Diseases

OpenAIRE

COJOCARU, Inimioara Mihaela; COJOCARU, Manole; SILOSI, Isabela; VRABIE, Camelia Doina

2014-01-01

The peripheral nervous system refers to parts of the nervous system outside the brain and spinal cord. Systemic autoimmune diseases can affect both the central and peripheral nervous systems in a myriad of ways and through a heterogeneous number of mechanisms leading to many different clinical manifestations. As a result, neurological complications of these disorders can result in significant morbidity and mortality. The most common complication of peripheral nervous system (PNS) involvement ...

Multibody Systems

DEFF Research Database (Denmark)

Wagner, Falko Jens

1999-01-01

Multibody Systems is one area, in which methods for solving DAEs are of special interst. This chapter is about multibody systems, why they result in DAE systems and what kind of problems that can arise when dealing with multibody systems and formulating their corresponding DAE system....

Engineering Elegant Systems: Postulates, Principles, and Hypotheses of Systems Engineering

Science.gov (United States)

Watson, Michael D.

2018-01-01

Definition: System Engineering is the engineering discipline which integrates the system functions, system environment, and the engineering disciplines necessary to produce and/or operate an elegant system; Elegant System - A system that is robust in application, fully meeting specified and adumbrated intent, is well structured, and is graceful in operation. Primary Focus: System Design and Integration: Identify system couplings and interactions; Identify system uncertainties and sensitivities; Identify emergent properties; Manage the effectiveness of the system. Engineering Discipline Integration: Manage flow of information for system development and/or operations; Maintain system activities within budget and schedule. Supporting Activities: Process application and execution.

Applying System of Systems Engineering(SoSE) to VIVO?

OpenAIRE

Wang, Jing

2015-01-01

System of systems (SoS) refers to a set of operational and managerial independent systems interacting with each other to provide capabilities which cannot be accomplished by any single system. SoS has its own characteristics and challenges, such as emergent behavior and evolutionary development. This presentation will: Introduce the concepts and characteristics of system of systems (SoS) and system thinking practice. discuss SoS challenges using SoS case studies such as Global Earth Observati...

Systems integration.

Science.gov (United States)

Siemieniuch, C E; Sinclair, M A

2006-01-01

The paper presents a view of systems integration, from an ergonomics/human factors perspective, emphasising the process of systems integration as is carried out by humans. The first section discusses some of the fundamental issues in systems integration, such as the significance of systems boundaries, systems lifecycle and systems entropy, issues arising from complexity, the implications of systems immortality, and so on. The next section outlines various generic processes for executing systems integration, to act as guides for practitioners. These address both the design of the system to be integrated and the preparation of the wider system in which the integration will occur. Then the next section outlines some of the human-specific issues that would need to be addressed in such processes; for example, indeterminacy and incompleteness, the prediction of human reliability, workload issues, extended situation awareness, and knowledge lifecycle management. For all of these, suggestions and further readings are proposed. Finally, the conclusions section reiterates in condensed form the major issues arising from the above.

Formal heterogeneous system modeling with SystemC

DEFF Research Database (Denmark)

Niaki, Seyed Hosein Attarzadeh; Jakobsen, Mikkel Koefoed; Sulonen, Tero

2012-01-01

Electronic System Level (ESL) design of embedded systems proposes raising the abstraction level of the design entry to cope with the increasing complexity of such systems. To exploit the benefits of ESL, design languages should allow specification of models which are a) heterogeneous, to describe...

System description of the Repository-Only System for the FY 1990 systems integration program studies

International Nuclear Information System (INIS)

McKee, R.W.; Young, J.R.; Konzek, G.J.

1991-07-01

This document provides both functional and physical descriptions of a conceptual high-level waste management system defined as a Repository-Only System. Its purpose is to provide a basis for required system computer modeling and system studies initiated in FY 1990 under the Systems Integration Program of the US Department of Energy's (DOE) Office of Civilian Radioactive Waste Management (OCRWM). The Repository-Only System is designed to accept 3000 MTU per year of spent fuel and 400 equivalent MTU per year of high-level wastes disposal in the geologic repository. This document contains both functional descriptions of the processes in the waste management system and physical descriptions of the equipment and facilities necessary for performance of those processes. These descriptions contain the level of detail needed for the projected systems analysis studies. The Repository-Only System contains all system components, from the waste storage facilities of the waste generators to the underground facilities for final disposal of the wastes. The major facilities in the system are the waste generator waste storage facilities, a repository facility that packages the wastes and than emplaces them in the geologic repository, and the transportation equipment and facilities for transporting the wastes between these major facilities. 18 refs., 39 figs

Tank waste remediation system systems engineering management plan

International Nuclear Information System (INIS)

Peck, L.G.

1998-01-01

This Systems Engineering Management Plan (SEMP) describes the Tank Waste Remediation System (TWRS) implementation of the US Department of Energy (DOE) systems engineering policy provided in 97-IMSD-193. The SEMP defines the products, process, organization, and procedures used by the TWRS Project to implement the policy. The SEMP will be used as the basis for tailoring the systems engineering applications to the development of the physical systems and processes necessary to achieve the desired end states of the program. It is a living document that will be revised as necessary to reflect changes in systems engineering guidance as the program evolves. The US Department of Energy-Headquarters has issued program management guidance, DOE Order 430. 1, Life Cycle Asset Management, and associated Good Practice Guides that include substantial systems engineering guidance

JOSHUA system

International Nuclear Information System (INIS)

Honeck, H.C.

1975-04-01

A major computational system called JOSHUA has been under development at the Savannah River Laboratory since 1968. The JOSHUA System has two major parts: the Operating System and the Application System. The Operating System has been in production use since 1970 and provides data management, terminal, and job execution facilities. The Application System uses these facilities in solving problems in reactor physics and engineering. Features of the Application System are the two-dimensional lattice physics and three-dimensional transient reactor physics capabilities, which have been in use since 1971 and 1974, respectively. The capabilities of the JOSHUA System are summarized, and statistics on size, use, and development effort are provided. (U.S.)

Integrating system safety into the basic systems engineering process

Science.gov (United States)

Griswold, J. W.

1971-01-01

The basic elements of a systems engineering process are given along with a detailed description of what the safety system requires from the systems engineering process. Also discussed is the safety that the system provides to other subfunctions of systems engineering.

A behavioral framework for compositionality: linear systems, discrete event systems and hybrid systems

NARCIS (Netherlands)

Anak Agung Julius, A.A.J.; van der Schaft, Arjan

2004-01-01

In this paper we formulate a general framework based on the behavioral approach to dynamical systems, in which various issues regarding interconnection of systems can be addressed. The main part of the framework is that interconnections or compositions of systems can be modelled with interconnection

The Creation of Differential Correction Systems and the Systems of Global Navigation Satellite System Monitoring

National Research Council Canada - National Science Library

Polishchuk, G. M; Kozlov, V. I; Urlichich, Y. M; Dvorkin, V. V; Gvozdev, V. V

2002-01-01

... for the Russian Federation and a system of global navigation satellite system monitoring. These projects are some of the basic ones in the Federal program "Global Navigation System," aimed at maintenance and development of the GLONASS system...

Solar power satellite system; Uchu hatsuden system

Energy Technology Data Exchange (ETDEWEB)

Sasaki, S [Institute of Space and Astronautical Science, Tokyo (Japan)

1995-09-05

The solar power satellite system is a system that converts solar energy into electric energy in the space, transmits power to earth through wireless resort such as microwave and supplies energy of new concept. In order to realize this system it is necessary to have new technologies such as space power transmission at low cost, construction of large space buildings and wireless high power transmission. In this paper, the principles, characteristics and the necessary technology of this system were explained. Besides Japan`s SPS2000 Plan (cooperative research by universities, government agencies and private corporations on the model of solar power satellite) the group of Europe, Russia and the United States has also proposed some ideas concerning the solar power satellite system. As far as the microwave power transmission, which is the key technology for solar power satellite system, is concerned, ground demonstration tests at the level of several tens of kW are discussed in Canada and France. 3 refs., 3 figs.

System Analysis and Risk Assessment (SARA) system

International Nuclear Information System (INIS)

Krantz, E.A.; Russell, K.D.; Stewart, H.D.; Van Siclen, V.S.

1986-01-01

Utilization of Probabilistic Risk Assessment (PRA) related information in the day-to-day operation of plant systems has, in the past, been impracticable due to the size of the computers needed to run PRA codes. This paper discusses a microcomputer-based database system which can greatly enhance the capability of operators or regulators to incorporate PRA methodologies into their routine decision making. This system is called the System Analysis and Risk Assessment (SARA) system. SARA was developed by EG and G Idaho, Inc. at the Idaho National Engineering Laboratory to facilitate the study of frequency and consequence analyses of accident sequences from a large number of light water reactors (LWRs) in this country. This information is being amassed by several studies sponsored by the United States Nuclear Regulatory Commission (USNRC). To meet the need of portability and accessibility, and to perform the variety of calculations necessary, it was felt that a microcomputer-based system would be most suitable

Dynamic Systems Modeling in Educational System Design & Policy

Science.gov (United States)

Groff, Jennifer Sterling

2013-01-01

Over the last several hundred years, local and national educational systems have evolved from relatively simple systems to incredibly complex, interdependent, policy-laden structures, to which many question their value, effectiveness, and direction they are headed. System Dynamics is a field of analysis used to guide policy and system design in…

Optimization of large-scale heterogeneous system-of-systems models.

Energy Technology Data Exchange (ETDEWEB)

Parekh, Ojas; Watson, Jean-Paul; Phillips, Cynthia Ann; Siirola, John; Swiler, Laura Painton; Hough, Patricia Diane (Sandia National Laboratories, Livermore, CA); Lee, Herbert K. H. (University of California, Santa Cruz, Santa Cruz, CA); Hart, William Eugene; Gray, Genetha Anne (Sandia National Laboratories, Livermore, CA); Woodruff, David L. (University of California, Davis, Davis, CA)

2012-01-01

Decision makers increasingly rely on large-scale computational models to simulate and analyze complex man-made systems. For example, computational models of national infrastructures are being used to inform government policy, assess economic and national security risks, evaluate infrastructure interdependencies, and plan for the growth and evolution of infrastructure capabilities. A major challenge for decision makers is the analysis of national-scale models that are composed of interacting systems: effective integration of system models is difficult, there are many parameters to analyze in these systems, and fundamental modeling uncertainties complicate analysis. This project is developing optimization methods to effectively represent and analyze large-scale heterogeneous system of systems (HSoS) models, which have emerged as a promising approach for describing such complex man-made systems. These optimization methods enable decision makers to predict future system behavior, manage system risk, assess tradeoffs between system criteria, and identify critical modeling uncertainties.

System Design of the SWRL Financial System.

Science.gov (United States)

Ikeda, Masumi

To produce various management and accounting reports in order to maintain control of SWRL (Southwest Regional Laboratory) operational and financial activities, a computer-based SWRL financial system was developed. The system design is outlined, and various types of system inputs described. The kinds of management and accounting reports generated…

Test System Impact on System Availability

DEFF Research Database (Denmark)

Pau, L. F.

1987-01-01

The specifications are presented for an imperfect automatic test system (ATS) (test frequency distribution, reliability, false alarm rate, nondetection rate) in order to account for the availability, readiness, mean time between unscheduled repairs (MTBUR), reliability, and maintenance of the sys......The specifications are presented for an imperfect automatic test system (ATS) (test frequency distribution, reliability, false alarm rate, nondetection rate) in order to account for the availability, readiness, mean time between unscheduled repairs (MTBUR), reliability, and maintenance...... of the system subject to monitoring and test. A time-dependent Markov model is presented, and applied in three cases, with examples of numerical results provided for preventive maintenance decisions, design of an automatic test system, buffer testing in computers, and data communications....

Cognitive Systems

DEFF Research Database (Denmark)

The tutorial will discuss the definition of cognitive systems as the possibilities to extend the current systems engineering paradigm in order to perceive, learn, reason and interact robustly in open-ended changing environments. I will also address cognitive systems in a historical perspective...... to be modeled within a limited set of predefined specifications. There will inevitably be a need for robust decisions and behaviors in novel situations that include handling of conflicts and ambiguities based on the capability and knowledge of the artificial cognitive system. Further, there is a need...... in cognitive systems include e.g. personalized information systems, sensor network systems, social dynamics system and Web2.0, and cognitive components analysis. I will use example from our own research and link to other research activities....

What Is Energy Systems Integration? | Energy Systems Integration Facility |

Science.gov (United States)

NREL What Is Energy Systems Integration? What Is Energy Systems Integration? Energy systems integration (ESI) is an approach to solving big energy challenges that explores ways for energy systems to Research Community NREL is a founding member of the International Institute for Energy Systems Integration

MARBLE: A system for executing expert systems in parallel

Science.gov (United States)

Myers, Leonard; Johnson, Coe; Johnson, Dean

1990-01-01

This paper details the MARBLE 2.0 system which provides a parallel environment for cooperating expert systems. The work has been done in conjunction with the development of an intelligent computer-aided design system, ICADS, by the CAD Research Unit of the Design Institute at California Polytechnic State University. MARBLE (Multiple Accessed Rete Blackboard Linked Experts) is a system of C Language Production Systems (CLIPS) expert system tool. A copied blackboard is used for communication between the shells to establish an architecture which supports cooperating expert systems that execute in parallel. The design of MARBLE is simple, but it provides support for a rich variety of configurations, while making it relatively easy to demonstrate the correctness of its parallel execution features. In its most elementary configuration, individual CLIPS expert systems execute on their own processors and communicate with each other through a modified blackboard. Control of the system as a whole, and specifically of writing to the blackboard is provided by one of the CLIPS expert systems, an expert control system.

System dynamics

International Nuclear Information System (INIS)

Kim, Do Hun; Mun, Tae Hun; Kim, Dong Hwan

1999-02-01

This book introduces systems thinking and conceptual tool and modeling tool of dynamics system such as tragedy of single thinking, accessible way of system dynamics, feedback structure and causal loop diagram analysis, basic of system dynamics modeling, causal loop diagram and system dynamics modeling, information delay modeling, discovery and application for policy, modeling of crisis of agricultural and stock breeding products, dynamic model and lesson in ecosystem, development and decadence of cites and innovation of education forward system thinking.

Thermal systems; Systemes thermiques

Energy Technology Data Exchange (ETDEWEB)

Lalot, S. [Valenciennes Univ. et du Hainaut Cambresis, LME, 59 (France); Lecoeuche, S. [Ecole des Mines de Douai, Dept. GIP, 59 - Douai (France)]|[Lille Univ. des Sciences et Technologies, 59 - Villeneuve d' Ascq (France); Ahmad, M.; Sallee, H.; Quenard, D. [CSTB, 38 - Saint Martin d' Heres (France); Bontemps, A. [Universite Joseph Fourier, LEGI/GRETh, 38 - Grenoble (France); Gascoin, N.; Gillard, P.; Bernard, S. [Laboratoire d' Energetique, Explosion, Structure, 18 - Bourges (France); Gascoin, N.; Toure, Y. [Laboratoire Vision et Robotique, 18 - Bourges (France); Daniau, E.; Bouchez, M. [MBDA, 18 - Bourges (France); Dobrovicescu, A.; Stanciu, D. [Bucarest Univ. Polytechnique, Faculte de Genie Mecanique (Romania); Stoian, M. [Reims Univ. Champagne Ardenne, Faculte des Sciences, UTAP/LTM, 51 (France); Bruch, A.; Fourmigue, J.F.; Colasson, S. [CEA Grenoble, Lab. Greth, 38 (France); Bontemps, A. [Universite Joseph Fourier, LEGI/GRETh, 38 - Grenoble (France); Voicu, I.; Mare, T.; Miriel, J. [Institut National des Sciences Appliquees (INSA), LGCGM, IUT, 35 - Rennes (France); Galanis, N. [Sherbrooke Univ., Genie Mecanique, QC (Canada); Nemer, M.; Clodic, D. [Ecole des Mines de Paris, Centre Energetique et Procedes, 75 (France); Lasbet, Y.; Auvity, B.; Castelain, C.; Peerhossaini, H. [Nantes Univ., Ecole Polytechnique, Lab. de Thermocinetiquede Nantes, UMR-CNRS 6607, 44 (France)

2005-07-01

This session about thermal systems gathers 26 articles dealing with: neural model of a compact heat exchanger; experimental study and numerical simulation of the thermal behaviour of test-cells with walls made of a combination of phase change materials and super-insulating materials; hydraulic and thermal modeling of a supercritical fluid with pyrolysis inside a heated channel: pre-dimensioning of an experimental study; energy analysis of the heat recovery devices of a cryogenic system; numerical simulation of the thermo-hydraulic behaviour of a supercritical CO{sub 2} flow inside a vertical tube; mixed convection inside dual-tube exchangers; development of a nodal approach with homogenization for the simulation of the brazing cycle of a heat exchanger; chaotic exchanger for the cooling of low temperature fuel cells; structural optimization of the internal fins of a cylindrical generator; a new experimental approach for the study of the local boiling inside the channels of exchangers with plates and fins; experimental study of the flow regimes of boiling hydrocarbons on a bundle of staggered tubes; energy study of heat recovery exchangers used in Claude-type refrigerating systems; general model of Carnot engine submitted to various operating constraints; the free pistons Stirling cogeneration system; natural gas supplied cogeneration system with polymer membrane fuel cell; influence of the CRN coating on the heat flux inside the tool during the wood unrolling process; transport and mixture of a passive scalar injected inside the wake of a Ahmed body; control of a laser welding-brazing process by infrared thermography; 2D self-adaptative method for contours detection: application to the images of an aniso-thermal jet; exergy and exergy-economical study of an 'Ericsson' engine-based micro-cogeneration system; simplified air-conditioning of telephone switching equipments; parametric study of the 'low-energy' individual dwelling; brief synthesis of

Embedded Systems

Indian Academy of Sciences (India)

Embedded system, micro-con- troller ... Embedded systems differ from general purpose computers in many ... Low cost: As embedded systems are extensively used in con- .... operating systems for the desktop computers where scheduling.

Understanding Patterns for System-of-Systems Integration

DEFF Research Database (Denmark)

Kazman, Rick; Nielsen, Claus Ballegård; Schmid, Klaus

Creating a successful system of systems—one that meets the needs of its stakeholders today and can evolve and scale to sustain those stakeholders into the future—is a very complex engineering challenge. In a system of systems (SoS), one of the biggest challenges is in achieving cooperation and in...

Cold Vacuum Drying (CVD) Facility Vacuum Purge System Chilled Water System Design Description. System 47-4

International Nuclear Information System (INIS)

IRWIN, J.J.

2000-01-01

This system design description (SDD) addresses the Vacuum Purge System Chilled Water (VPSCHW) system. The discussion that follows is limited to the VPSCHW system and its interfaces with associated systems. The reader's attention is directed to Drawings H-1-82162, Cold Vacuum Drying Facility Process Equipment Skid PandID Vacuum System, and H-1-82224, Cold Vacuum Drying Facility Mechanical Utilities Process Chilled Water PandID. Figure 1-1 shows the location and equipment arrangement for the VPSCHW system. The VPSCHW system provides chilled water to the Vacuum Purge System (VPS). The chilled water provides the ability to condense water from the multi-canister overpack (MCO) outlet gases during the MCO vacuum and purge cycles. By condensing water from the MCO purge gas, the VPS can assist in drying the contents of the MCO

Power system protection 2 systems and methods

CERN Document Server

1995-01-01

The worldwide growth in demand for electricity has forced the pace of developments in electrical power system design to meet consumer needs for reliable, secure and cheap supplies. Power system protection, as a technology essential to high quality supply, is widely recognised as a specialism of growing and often critical importance, in which power system needs and technological progress have combined to result in rapid developments in policy and practice in recent years. In the United Kingdom, the need for appropriate training in power system protection was recognised in the early 1960s with t

Degradable Systems: A Survey of Multistate System Theory.

Science.gov (United States)

1982-08-01

and Subtitle) S. TYPE OF REPORT & PERIOD COVERED C. O DEGRADABLE SYSTEMS: A SURVEY OF MULTISTATE TECHNICAL SYSTEM THEORY 6. PERFORMING ORG. REPORT...THIS PAGE(R7,en Date £nt.,.d) AEoS-T- 8- 9 2 0 Degradable Systems: A Survey of Multistate System Theory by 1 2Emad El-Neweihi and Frank Proschan

Holographic representation of space-variant systems: system theory.

Science.gov (United States)

Marks Ii, R J; Krile, T F

1976-09-01

System theory for holographic representation of linear space-variant systems is derived. The utility of the resulting piecewise isoplanatic approximation (PIA) is illustrated by example application to the invariant system, ideal magnifier, and Fourier transformer. A method previously employed to holographically represent a space-variant system, the discrete approximation, is shown to be a special case of the PIA.

General Systems Theory and Instructional Systems Design.

Science.gov (United States)

Salisbury, David F.

1990-01-01

Describes basic concepts in the field of general systems theory (GST) and identifies commonalities that exist between GST and instructional systems design (ISD). Models and diagrams that depict system elements in ISD are presented, and two matrices that show how GST has been used in ISD literature are included. (11 references) (LRW)

Construction of test-bed system of voltage management system to ...

African Journals Online (AJOL)

Construction of test-bed system of voltage management system to apply physical power system. ... Journal of Fundamental and Applied Sciences ... system of voltage management system (VMS) in order to apply physical power system.

Next generation railway system. ; Control system for JR Maglev. Jisedai tetsudo system. ; Rinia shinkansen no seigyo system

Energy Technology Data Exchange (ETDEWEB)

Matsuda, K [Central Japan Railway Company, Nagoya (Japan)

1993-07-10

Aiming at achieving a maglev Shinkansen that links Tokyo with Osaka at a speed of 500 km/h, an experimental maglev line is being constructed in Yamanashi Prefecture. This paper explains a train control system as the main subject. The system mounts superconductive magnets directly on bogies to propel a train using actions of moving magnet fields generated from propulsion coils paved on ground. Because of its mechanism to levitate and guide the train using induction coils superposed on the propulsion coils, no special control device is required for the levitation and guidance. This is a difference from a normal conduction magnet levitation system. Its speed control also differs from the conventional railway systems. It uses a ground primary control system that controls supply currents from substations on the ground, including braking control. One substation controls one train only. Automatic control is made on all controls related to travelling, including a control from train movement start to stops at predetermined positions, scheduled-time operation control, and jerk control. The construction of the experimental line is under steady progress. 5 figs.

78 FR 18252 - Prevailing Rate Systems; North American Industry Classification System Based Federal Wage System...

Science.gov (United States)

2013-03-26

...-AM78 Prevailing Rate Systems; North American Industry Classification System Based Federal Wage System... applicable sections. The Federal Prevailing Rate Advisory Committee, the national labor- management committee... proposing to amend 5 CFR part 532 as follows: PART 532--PREVAILING RATE SYSTEMS 0 1. The authority citation...

Systems engineering simplified

CERN Document Server

Cloutier, Robert; Bone, Mary Alice

2015-01-01

IntroductionOverviewDiscussion of Common TerminologyThe Case for Systems EngineeringA Brief History of Systems EngineeringSystem ExamplesSummaryThe System Life CycleManaging System Development-The Vee ModelSystem ProductionSystem Utilization and SupportSystem Retirement and DisposalOther Systems Engineering Development ModelsSpiral ModelAgile Model for Systems EngineeringSystem of InterestAbstraction and DecompositionIntegrationDeveloping and Managing RequirementsCyclone Requiremen

Expert Systems for auditing management information systems

Directory of Open Access Journals (Sweden)

Gheroghe Popescu

2007-05-01

Full Text Available Expert systems are built with the help of: specialised programming languages or expert system generators (shell. But this structure was reached after tens of years of work and research, because expert systems are nothing but pragmatic capitalisation of the results of research carried out in artificial intelligence and theory of knowledge.

System and method for creating expert systems

Science.gov (United States)

Hughes, Peter M. (Inventor); Luczak, Edward C. (Inventor)

1998-01-01

A system and method provides for the creation of a highly graphical expert system without the need for programming in code. An expert system is created by initially building a data interface, defining appropriate Mission, User-Defined, Inferred, and externally-generated GenSAA (EGG) data variables whose data values will be updated and input into the expert system. Next, rules of the expert system are created by building appropriate conditions of the rules which must be satisfied and then by building appropriate actions of rules which are to be executed upon corresponding conditions being satisfied. Finally, an appropriate user interface is built which can be highly graphical in nature and which can include appropriate message display and/or modification of display characteristics of a graphical display object, to visually alert a user of the expert system of varying data values, upon conditions of a created rule being satisfied. The data interface building, rule building, and user interface building are done in an efficient manner and can be created without the need for programming in code.

Bitcoin System

Directory of Open Access Journals (Sweden)

Jan Lánský

2017-06-01

Full Text Available Cryptocurrency systems are purely digital and decentralized systems that use cryptographic principles to confirm transactions. Bitcoin is the first and also the most widespread cryptocurrency. The aim of this article is to introduce Bitcoin system using a language understandable also to readers without computer science education. This article captures the Bitcoin system from three perspectives: internal structure, network and users. Emphasis is placed on brief and clear definitions (system components and their mutual relationships. A new system view of the stated terms constitutes author’s own contribution.

Waste receiving and processing plant control system; system design description

Energy Technology Data Exchange (ETDEWEB)

LANE, M.P.

1999-02-24

The Plant Control System (PCS) is a heterogeneous computer system composed of numerous sub-systems. The PCS represents every major computer system that is used to support operation of the Waste Receiving and Processing (WRAP) facility. This document, the System Design Description (PCS SDD), includes several chapters and appendices. Each chapter is devoted to a separate PCS sub-system. Typically, each chapter includes an overview description of the system, a list of associated documents related to operation of that system, and a detailed description of relevant system features. Each appendice provides configuration information for selected PCS sub-systems. The appendices are designed as separate sections to assist in maintaining this document due to frequent changes in system configurations. This document is intended to serve as the primary reference for configuration of PCS computer systems. The use of this document is further described in the WRAP System Configuration Management Plan, WMH-350, Section 4.1.

Waste receiving and processing plant control system; system design description

International Nuclear Information System (INIS)

LANE, M.P.

1999-01-01

The Plant Control System (PCS) is a heterogeneous computer system composed of numerous sub-systems. The PCS represents every major computer system that is used to support operation of the Waste Receiving and Processing (WRAP) facility. This document, the System Design Description (PCS SDD), includes several chapters and appendices. Each chapter is devoted to a separate PCS sub-system. Typically, each chapter includes an overview description of the system, a list of associated documents related to operation of that system, and a detailed description of relevant system features. Each appendice provides configuration information for selected PCS sub-systems. The appendices are designed as separate sections to assist in maintaining this document due to frequent changes in system configurations. This document is intended to serve as the primary reference for configuration of PCS computer systems. The use of this document is further described in the WRAP System Configuration Management Plan, WMH-350, Section 4.1

Supporting Space Systems Design via Systems Dependency Analysis Methodology

Science.gov (United States)

Guariniello, Cesare

The increasing size and complexity of space systems and space missions pose severe challenges to space systems engineers. When complex systems and Systems-of-Systems are involved, the behavior of the whole entity is not only due to that of the individual systems involved but also to the interactions and dependencies between the systems. Dependencies can be varied and complex, and designers usually do not perform analysis of the impact of dependencies at the level of complex systems, or this analysis involves excessive computational cost, or occurs at a later stage of the design process, after designers have already set detailed requirements, following a bottom-up approach. While classical systems engineering attempts to integrate the perspectives involved across the variety of engineering disciplines and the objectives of multiple stakeholders, there is still a need for more effective tools and methods capable to identify, analyze and quantify properties of the complex system as a whole and to model explicitly the effect of some of the features that characterize complex systems. This research describes the development and usage of Systems Operational Dependency Analysis and Systems Developmental Dependency Analysis, two methods based on parametric models of the behavior of complex systems, one in the operational domain and one in the developmental domain. The parameters of the developed models have intuitive meaning, are usable with subjective and quantitative data alike, and give direct insight into the causes of observed, and possibly emergent, behavior. The approach proposed in this dissertation combines models of one-to-one dependencies among systems and between systems and capabilities, to analyze and evaluate the impact of failures or delays on the outcome of the whole complex system. The analysis accounts for cascading effects, partial operational failures, multiple failures or delays, and partial developmental dependencies. The user of these methods can

Embedded systems handbook networked embedded systems

CERN Document Server

Zurawski, Richard

2009-01-01

Considered a standard industry resource, the Embedded Systems Handbook provided researchers and technicians with the authoritative information needed to launch a wealth of diverse applications, including those in automotive electronics, industrial automated systems, and building automation and control. Now a new resource is required to report on current developments and provide a technical reference for those looking to move the field forward yet again. Divided into two volumes to accommodate this growth, the Embedded Systems Handbook, Second Edition presents a comprehensive view on this area

Modern system architectures in embedded systems

International Nuclear Information System (INIS)

Korhonen, T.

2012-01-01

Several new technologies are making their way also in embedded systems. In addition to the FPGA technology which has become commonplace, multi-core CPUs and I/O virtualization (the implementation of the tasks of a software hyper-visor in hardware to improve the efficiency) are being introduced to the embedded systems. In this paper we review the trends and discuss how to take advantage of these features in control systems. Some potential application examples like parallelization, data streaming, high-speed data acquisition and virtualization are discussed

Nonlinearity of colloid systems oxyhydrate systems

CERN Document Server

Sucharev, Yuri I

2008-01-01

The present monograph is the first systematic study of the non-linear characteristic of gel oxy-hydrate systems involving d- and f- elements. These are the oxyhydrates of rare-earth elements and oxides - hydroxides of d- elements (zirconium, niobium, titanium, etc.) The non-linearity of these gel systems introduces fundamental peculiarities into their structure and, consequently, their properties. The polymer-conformational diversity of energetically congenial gel fragments, which continu-ously transform under the effect of, for instance, system dissipation heat, is central to the au-thor's hy

Systems of Systems: Scaling up the Development Program

National Research Council Canada - National Science Library

Humphrey, Watts

2006-01-01

... into system-of-systems structures. Section 3 points out how large-scale systems development efforts have typically failed because of project-management and not technical problems, and that the solutions to these problems...

COGNITIVE SYSTEMS. REDEFINING THE COOPERATION BETWEEN MAN AND SYSTEM

Directory of Open Access Journals (Sweden)

Diana-Aderina MOISUC

2016-12-01

Full Text Available Cognitive systems appeared as a response to the real challenges brought by the Big Data phenomenon. It was found that the solutions for solving difficult problems caused by this phenomenon could be brought by using artificial intelligence tools. In this context a convergence between Big Data and Artificial Intelligence happened, which determined the start of a new stage in system development, namely the era of cognitive systems. The potential of these systems is given by the characteristics that differentiate them from other systems. The cognitive systems offered solutions and were used with success in complex projects from the medical and financial sectors. The architecture of cognitive systems is complex. These systems are designed so that they use artificial intelligence tools when processing source content, producing analytical solutions which can be used in the decision process. In this paper base concepts, the characteristics and architecture of cognitive systems, the benefits brought by the development and use of them were presented.

Systems effectiveness

CERN Document Server

Habayeb, A R

1987-01-01

Highlights three principal applications of system effectiveness: hardware system evaluation, organizational development and evaluation, and conflict analysis. The text emphasizes the commonality of the system effectiveness discipline. The first part of the work presents a framework for system effectiveness, partitioning and hierarchy of hardware systems. The second part covers the structure, hierarchy, states, functions and activities of organizations. Contains an extended Appendix on mathematical concepts and also several project suggestions.

Auxiliary systems

International Nuclear Information System (INIS)

Meyer, P.J.

1981-01-01

Systems included under the heading ''Reactor Auxillary Systems'' are those immediately involved with the reactor operation. These include the systems for dosing and letdown of reactor coolant, as well as for the chemical dosing, purification and treatment of the reactor coolant and the cooling system in the controlled area. The ancillary systems are mainly responsible for liquid and gaseous treatment and the waste treatment for final storage. (orig.)

Situation Awareness with Systems of Systems

NARCIS (Netherlands)

Laar, P. van de; Tretmans, J.; Borth, M.

2013-01-01

This book discusses various aspects, challenges, and solutions for developing systems-of-systems for situation awareness, using applications in the domain of maritime safety and security. Topics include advanced, multi-objective visualization methods for situation awareness, stochastic outlier

3S - Systematic, systemic, and systems biology and toxicology.

Science.gov (United States)

Smirnova, Lena; Kleinstreuer, Nicole; Corvi, Raffaella; Levchenko, Andre; Fitzpatrick, Suzanne C; Hartung, Thomas

2018-01-01

A biological system is more than the sum of its parts - it accomplishes many functions via synergy. Deconstructing the system down to the molecular mechanism level necessitates the complement of reconstructing functions on all levels, i.e., in our conceptualization of biology and its perturbations, our experimental models and computer modelling. Toxicology contains the somewhat arbitrary subclass "systemic toxicities"; however, there is no relevant toxic insult or general disease that is not systemic. At least inflammation and repair are involved that require coordinated signaling mechanisms across the organism. However, the more body components involved, the greater the challenge to reca-pitulate such toxicities using non-animal models. Here, the shortcomings of current systemic testing and the development of alternative approaches are summarized. We argue that we need a systematic approach to integrating existing knowledge as exemplified by systematic reviews and other evidence-based approaches. Such knowledge can guide us in modelling these systems using bioengineering and virtual computer models, i.e., via systems biology or systems toxicology approaches. Experimental multi-organ-on-chip and microphysiological systems (MPS) provide a more physiological view of the organism, facilitating more comprehensive coverage of systemic toxicities, i.e., the perturbation on organism level, without using substitute organisms (animals). The next challenge is to establish disease models, i.e., micropathophysiological systems (MPPS), to expand their utility to encompass biomedicine. Combining computational and experimental systems approaches and the chal-lenges of validating them are discussed. The suggested 3S approach promises to leverage 21st century technology and systematic thinking to achieve a paradigm change in studying systemic effects.

Smart power systems and renewable energy system integration

CERN Document Server

2016-01-01

This monograph presents a wider spectrum of researches, developments, and case specific studies in the area of smart power systems and integration of renewable energy systems. The book will be for the benefit of a wider audience including researchers, postgraduate students, practicing engineers, academics, and regulatory policy makers. It covers a wide range of topics from fundamentals, and modelling and simulation aspects of traditional and smart power systems to grid integration of renewables; Micro Grids; challenges in planning and operation of a smart power system; risks, security, and stability in smart operation of a power system; and applied research in energy storage. .

An algebraic method for system reduction of stationary Gaussian systems

NARCIS (Netherlands)

D. Jibetean; J.H. van Schuppen (Jan)

2003-01-01

textabstractSystem identification for a particular approach reduces to system reduction, determining for a system with a high state-space dimension a system of low state-space dimension. For Gaussian systems the problem of system reduction is considered with the divergence rate criterion. The

Open systems dependability dependability engineering for ever-changing systems

CERN Document Server

Tokoro, Mario

2015-01-01

The book describes a fundamentally new approach to software dependability, considering a software system as an ever-changing system due to changes in service objectives, users' requirements, standards and regulations, and to advances in technology. Such a system is viewed as an Open System since its functions, structures, and boundaries are constantly changing. Thus, the approach to dependability is called Open Systems Dependability. The DEOS technology realizes Open Systems Dependability. It puts more emphasis on stakeholders' agreement and accountability achievement for business/service cont

System of Systems Analytic Workbench - 2017

Science.gov (United States)

2017-08-31

Genetic Algorithm and Particle Swarm Optimization with Type-2 Fuzzy Sets for Generating Systems of Systems Architectures. Procedia Computer Science...The application effort involves modeling an existing messaging network to perform real-time situational awareness. The Analytical Workbench’s

Genetic association of the KLK4 locus with risk of prostate cancer.

Directory of Open Access Journals (Sweden)

Felicity Lose

Full Text Available The Kallikrein-related peptidase, KLK4, has been shown to be significantly overexpressed in prostate tumours in numerous studies and is suggested to be a potential biomarker for prostate cancer. KLK4 may also play a role in prostate cancer progression through its involvement in epithelial-mesenchymal transition, a more aggressive phenotype, and metastases to bone. It is well known that genetic variation has the potential to affect gene expression and/or various protein characteristics and hence we sought to investigate the possible role of single nucleotide polymorphisms (SNPs in the KLK4 gene in prostate cancer. Assessment of 61 SNPs in the KLK4 locus (± 10 kb in approximately 1300 prostate cancer cases and 1300 male controls for associations with prostate cancer risk and/or prostate tumour aggressiveness (Gleason score <7 versus ≥ 7 revealed 7 SNPs to be associated with a decreased risk of prostate cancer at the P(trend<0.05 significance level. Three of these SNPs, rs268923, rs56112930 and the HapMap tagSNP rs7248321, are located several kb upstream of KLK4; rs1654551 encodes a non-synonymous serine to alanine substitution at position 22 of the long isoform of the KLK4 protein, and the remaining 3 risk-associated SNPs, rs1701927, rs1090649 and rs806019, are located downstream of KLK4 and are in high linkage disequilibrium with each other (r(2 ≥ 0.98. Our findings provide suggestive evidence of a role for genetic variation in the KLK4 locus in prostate cancer predisposition.

Prostate-Specific Antigen (PSA) Screening and New Biomarkers for Prostate Cancer (PCa).

Science.gov (United States)

Stephan, Carsten; Rittenhouse, Harry; Hu, Xinhai; Cammann, Henning; Jung, Klaus

2014-04-01

PSA screening reduces PCa-mortality but the disadvantages overdiagnosis and overtreatment require multivariable risk-prediction tools to select appropriate treatment or active surveillance. This review explains the differences between the two largest screening trials and discusses the drawbacks of screening and its meta-analysisxs. The current American and European screening strategies are described. Nonetheless, PSA is one of the most widely used tumor markers and strongly correlates with the risk of harboring PCa. However, while PSA has limitations for PCa detection with its low specificity there are several potential biomarkers presented in this review with utility for PCa currently being studied. There is an urgent need for new biomarkers especially to detect clinically significant and aggressive PCa. From all PSA-based markers, the FDA-approved prostate health index (phi) shows improved specificity over percent free and total PSA. Another kallikrein panel, 4K, which includes KLK2 has recently shown promise in clinical research studies but has not yet undergone formal validation studies. In urine, prostate cancer gene 3 (PCA3) has also been validated and approved by the FDA for its utility to detect PCa. The potential correlation of PCA3 with cancer aggressiveness requires more clinical studies. The detection of the fusion of androgen-regulated genes with genes of the regulatory transcription factors in tissue of (~)50% of all PCa-patients is a milestone in PCa research. A combination of the urinary assays for TMPRSS2:ERG gene fusion and PCA3 shows an improved accuracy for PCa detection. Overall, the field of PCa biomarker discovery is very exciting and prospective.

Diabetic Macular Edema: Current Understanding, Pharmacologic Treatment Options, and Developing Therapies.

Science.gov (United States)

Miller, Kevin; Fortun, Jorge A

2018-01-01

Diabetic retinopathy and diabetic macular edema comprise a major source of visual disability throughout the developed world. The etiology and pathogenesis of macular edema is intricate and multifactorial, in which the hyperglycemic state in diabetes induces a microangiopathy. Through several inflammatory and vasogenic mediators, including vascular endothelial growth factor (VEGF) upregulation and inflammatory cytokines and chemokines, pathologic changes are induced in the vascular endothelium triggering breakdown of the blood retinal barrier, causing extravasation of fluid into the extracellular space and manifesting clinically as macular edema, resulting in visual loss. The advent of medications targeting the VEGF pathway has led to great clinical improvements compared with the previous standard of care of laser therapy alone, as shown in studies such as RISE, RIDE, VIVID, VISTA, and DRCR. However, analyses have shown that many patients have inadequate response or are nonresponders to anti-VEGF therapy, demonstrating the need for additional therapies to more comprehensively treat this disease. Although corticosteroid treatments and implants have demonstrated some efficacy in adjunctive and supplemental treatment, the need to more adequately treat macular edema remains. Our knowledge of diabetic macular edema continues to grow, leading to new currently available and emerging pharmacotherapies to further enhance our treatment and restore vision in those affected by diabetic macular edema. This review will discuss the pathogenesis of diabetic macular edema and the pharmacologic therapies available for its treatment, including anti-VEGF, steroids, and newer therapies still in development, such as angiopoietin antagonists, Tie2 agonists, kallikrein inhibitors, interleukin inhibitors, and others. Copyright 2018 Asia-Pacific Academy of Ophthalmology.

The effects of IL-20 subfamily cytokines on reconstituted human epidermis suggest potential roles in cutaneous innate defense and pathogenic adaptive immunity in psoriasis.

Science.gov (United States)

Sa, Susan M; Valdez, Patricia A; Wu, Jianfeng; Jung, Kenneth; Zhong, Fiona; Hall, Linda; Kasman, Ian; Winer, Jane; Modrusan, Zora; Danilenko, Dimitry M; Ouyang, Wenjun

2007-02-15

IL-19, IL-20, IL-22, IL-24, and IL-26 are members of the IL-10 family of cytokines that have been shown to be up-regulated in psoriatic skin. Contrary to IL-10, these cytokines signal using receptor complex R1 subunits that are preferentially expressed on cells of epithelial origin; thus, we henceforth refer to them as the IL-20 subfamily cytokines. In this study, we show that primary human keratinocytes (KCs) express receptors for these cytokines and that IL-19, IL-20, IL-22, and IL-24 induce acanthosis in reconstituted human epidermis (RHE) in a dose-dependent manner. These cytokines also induce expression of the psoriasis-associated protein S100A7 and keratin 16 in RHE and cause persistent activation of Stat3 with nuclear localization. IL-22 had the most pronounced effects on KC proliferation and on the differentiation of KCs in RHE, inducing a decrease in the granular cell layer (hypogranulosis). Furthermore, gene expression analysis performed on cultured RHE treated with these cytokines showed that IL-19, IL-20, IL-22, and IL-24 regulate many of these same genes to variable degrees, inducing a gene expression profile consistent with inflammatory responses, wound healing re-epithelialization, and altered differentiation. Many of these genes have also been found to be up-regulated in psoriatic skin, including several chemokines, beta-defensins, S100 family proteins, and kallikreins. These results confirm that IL-20 subfamily cytokines are important regulators of epidermal KC biology with potentially pivotal roles in the immunopathology of psoriasis.

Chymase inhibition prevents fibronectin and myofibrillar loss and improves cardiomyocyte function and LV torsion angle in dogs with isolated mitral regurgitation.

Science.gov (United States)

Pat, Betty; Chen, Yuanwen; Killingsworth, Cheryl; Gladden, James D; Shi, Ke; Zheng, Junying; Powell, Pamela C; Walcott, Greg; Ahmed, Mustafa I; Gupta, Himanshu; Desai, Ravi; Wei, Chih-Chang; Hase, Naoki; Kobayashi, Tsunefumi; Sabri, Abdelkarim; Granzier, Henk; Denney, Thomas; Tillson, Michael; Dillon, A Ray; Husain, Ahsan; Dell'italia, Louis J

2010-10-12

The left ventricular (LV) dilatation of isolated mitral regurgitation (MR) is associated with an increase in chymase and a decrease in interstitial collagen and extracellular matrix. In addition to profibrotic effects, chymase has significant antifibrotic actions because it activates matrix metalloproteinases and kallikrein and degrades fibronectin. Thus, we hypothesize that chymase inhibitor (CI) will attenuate extracellular matrix loss and LV remodeling in MR. We studied dogs with 4 months of untreated MR (MR; n=9) or MR treated with CI (MR+CI; n=8). Cine MRI demonstrated a >40% increase in LV end-diastolic volume in both groups, consistent with a failure of CI to improve a 25% decrease in interstitial collagen in MR. However, LV cardiomyocyte fractional shortening was decreased in MR versus normal dogs (3.71±0.24% versus 4.81±0.31%; P<0.05) and normalized in MR+CI dogs (4.85±0.44%). MRI with tissue tagging demonstrated an increase in LV torsion angle in MR+CI versus MR dogs. CI normalized the significant decrease in fibronectin and FAK phosphorylation and prevented cardiomyocyte myofibrillar degeneration in MR dogs. In addition, total titin and its stiffer isoform were increased in the LV epicardium and paralleled the changes in fibronectin and FAK phosphorylation in MR+CI dogs. These results suggest that chymase disrupts cell surface-fibronectin connections and FAK phosphorylation that can adversely affect cardiomyocyte myofibrillar structure and function. The greater effect of CI on epicardial versus endocardial titin and noncollagen cell surface proteins may be responsible for the increase in torsion angle in chronic MR.

Proteolytic activity of prostate-specific antigen (PSA towards protein substrates and effect of peptides stimulating PSA activity.

Directory of Open Access Journals (Sweden)

Johanna M Mattsson

Full Text Available Prostate-specific antigen (PSA or kallikrein-related peptidase-3, KLK3 exerts chymotrypsin-like proteolytic activity. The main biological function of PSA is the liquefaction of the clot formed after ejaculation by cleavage of semenogelins I and II in seminal fluid. PSA also cleaves several other substrates, which may explain its putative functions in prostate cancer and its antiangiogenic activity. We compared the proteolytic efficiency of PSA towards several protein and peptide substrates and studied the effect of peptides stimulating the activity of PSA with these substrates. An endothelial cell tube formation model was used to analyze the effect of PSA-degraded protein fragments on angiogenesis. We showed that PSA degrades semenogelins I and II much more efficiently than other previously identified protein substrates, e.g., fibronectin, galectin-3 and IGFBP-3. We identified nidogen-1 as a new substrate for PSA. Peptides B2 and C4 that stimulate the activity of PSA towards small peptide substrates also enhanced the proteolytic activity of PSA towards protein substrates. Nidogen-1, galectin-3 or their fragments produced by PSA did not have any effect on endothelial cell tube formation. Although PSA cleaves several other protein substrates, in addition to semenogelins, the physiological importance of this activity remains speculative. The PSA levels in prostate are very high, but several other highly active proteases, such as hK2 and trypsin, are also expressed in the prostate and may cleave protein substrates that are weakly cleaved by PSA.

Eicosapentaenoic acid ameliorates non-alcoholic steatohepatitis in a novel mouse model using melanocortin 4 receptor-deficient mice.

Science.gov (United States)

Konuma, Kuniha; Itoh, Michiko; Suganami, Takayoshi; Kanai, Sayaka; Nakagawa, Nobutaka; Sakai, Takeru; Kawano, Hiroyuki; Hara, Mitsuko; Kojima, Soichi; Izumi, Yuichi; Ogawa, Yoshihiro

2015-01-01

Many attempts have been made to find novel therapeutic strategies for non-alcoholic steatohepatitis (NASH), while their clinical efficacy is unclear. We have recently reported a novel rodent model of NASH using melanocortin 4 receptor-deficient (MC4R-KO) mice, which exhibit the sequence of events that comprise hepatic steatosis, liver fibrosis, and hepatocellular carcinoma with obesity-related phenotypes. In the liver of MC4R-KO mice, there is a unique histological feature termed hepatic crown-like structures (hCLS), where macrophages interact with dead hepatocytes and fibrogenic cells, thereby accelerating inflammation and fibrosis. In this study, we employed MC4R-KO mice to examine the effect of highly purified eicosapentaenoic acid (EPA), a clinically available n-3 polyunsaturated fatty acid, on the development of NASH. EPA treatment markedly prevented the development of hepatocyte injury, hCLS formation and liver fibrosis along with lipid accumulation. EPA treatment was also effective even after MC4R-KO mice developed NASH. Intriguingly, improvement of liver fibrosis was accompanied by the reduction of hCLS formation and plasma kallikrein-mediated transforming growth factor-β activation. Moreover, EPA treatment increased the otherwise reduced serum concentrations of adiponectin, an adipocytokine with anti-inflammatory and anti-fibrotic properties. Collectively, EPA treatment effectively prevents the development and progression of NASH in MC4R-KO mice along with amelioration of hepatic steatosis. This study unravels a novel anti-fibrotic mechanism of EPA, thereby suggesting a clinical implication for the treatment of NASH.